0
In a clinical multicenter comparative study, the efficacy and safety of L-ornithine-L-aspartate (Hepa-Merz), which belongs to the group of hepatoprotective agents affecting metabolic disorders, was studied. The study included 232 patients with acute pancreatitis. It was found that L-ornithine-L-aspartate (Hepa-Merz) reduces the severity of neurological disorders in pancreatic necrosis. The drug has pronounced hepatoprotective properties.
According to the literature and our observations, the incidence of acute pancreatitis is steadily increasing, in frequency it ranks third after acute appendicitis and cholecystitis. Treatment of acute pancreatitis, especially its destructive forms, is still a difficult problem in surgery due to the high mortality rate - from 25 to 80%.
The liver turns out to be the first target organ, which accounts for the main blow of pancreatogenic toxemia in the form of a massive influx of activated pancreatic and lysosomal enzymes, biologically active substances, toxic decay products of the pancreatic parenchyma during necrobiosis and activation of the kallikrein-kinin system into the blood flowing through the portal vein.
As a result of the action of damaging factors in the liver parenchyma, deep microcirculatory disorders develop, in hepatocytes, mitochondrial cell death factors are activated and apoptosis of hepatic cells is induced. Decompensation of the internal mechanisms of detoxification aggravates the course of acute pancreatitis due to the accumulation of many toxic substances and metabolites in the body, which are concentrated in the blood and create a secondary hepatotropic effect.
Liver failure is one of the most serious complications of acute pancreatitis. It often determines the course of the disease and its outcome. It is known from the literature that in 20.6% of patients with edematous pancreatitis and in 78.7% of patients with a destructive process in the pancreas, various liver functions are impaired, which significantly worsens the results of treatment and is the direct cause of death in 72% of cases.
In view of this, the need for adequate prevention and treatment of hepatic failure in each patient with acute pancreatitis using the entire range of conservative measures is obvious. Today, one of the priority areas of complex therapy for liver failure in acute pancreatitis is the inclusion of hepatoprotectors in treatment, in particular L-ornithine-L-aspartate (Hepa-Merz).
The drug has existed on the pharmaceutical market for several years, it has proven itself well and is successfully used in therapeutic, neurological, toxicological practice for acute and chronic liver diseases. The drug stimulates the detoxification function of the liver, regulates metabolism in hepatocytes, and has a pronounced antioxidant effect.
In the period from November 2009 to March 2010, a multicenter non-randomized clinical study was carried out to study the effectiveness of the hepatoprotector L-ornithine-L-aspartate (Hepa-Merz) in the complex treatment of patients with acute pancreatitis. The study included 232 patients (150 (64.7%) men and 82 (35.3%) women) with acute pancreatitis, confirmed by clinical laboratory and instrumental methods. The age of the patients varied from 17 to 86 years, with an average of 46.7 (34; 58) years. In 156 (67.2%) patients, edematous pancreatitis was diagnosed, in 76 (32.8%) - destructive forms: in 21 (9.1%) - hemorrhagic pancreatic necrosis, in 13 (5.6%) - fatty, in 41 (17.7%) - mixed, 1 (0.4%) - post-traumatic.
All patients received basic complex conservative therapy (blockade of exocrine pancreatic function, infusion-detoxification, antibacterial agents).
L-ornithine-L-aspartate (Hepa-Merz) in a complex of therapeutic measures was used in 182 (78.4%) patients (main group); 50 (21.6%) patients made up the control group, in which this drug was not used. The drug was prescribed from the 1st day of the patient's inclusion in the study according to the developed scheme: 10 g (2 ampoules) intravenously with an injection rate of no more than 5 g / h per 400 ml of physiological sodium chloride solution for 5 days, from the 6th day - orally (preparation in the form of granules, 1 packet, 3 g, 3 times a day for 10 days).
The severity of the patient's condition was assessed using the SAPS II scale of the severity of the physiological condition. Depending on the total SAPS II score in both groups, 2 subgroups of patients were identified: with a total score<30 и >30.
Subgroup with severity according to SAPS II<30 баллов составили 112 (48,3%) пациентов, в том числе 97 (87%) - из основной группы: мужчин - 74 (76,3%), женщин - 23 (23,7%), средний возраст - 40,9 (33; 45) года, тяжесть состояния - 20,4±5,2 балла; из контрольной группы было 15 (13%) пациентов: мужчин - 11 (73,3%), женщин - 4 (26,7%), средний возраст - 43,3 (28,5; 53) года, тяжесть состояния - 25±6 баллов.
The subgroup with a total SAPS II score> 30 consisted of 120 (51.7%) patients, including 85 (71%) from the main group: men - 56 (65.9%), women - 29 (34.1%) ), the average age is 58.2 (45; 66.7) years, the severity of the condition is 36.3 + 5.6 points; from the control group there were 35 (29%) patients: men - 17 (48.5%), women - 18 (51.4%), average age - 55.4 (51; 63.5) years, severity of the condition - 39 , 3 ± 5.9 points.
The study identified 4 base points: 1st, 3rd, 5th and 15th days. To assess the effectiveness of treatment, the dynamics of the severity of the patient's condition was determined according to the SOFA Integral Scale; investigated laboratory parameters: the concentration of bilirubin, the level of protein, urea and creatinine, cytolysis enzymes - alanine aminotransferase (ALT), aspartate aminotransferase (ACT). The degree of impairment of cognitive functions and the rate of their recovery during treatment were assessed using the number link test (NNT).
Mathematical processing of the factual material was carried out using the basic methods of biomedical statistics using the Microsoft Office Excel 2003 and BIOSTAT software package. When describing group characteristics, the standard deviation of the mean value of the trait was calculated for its parametric distribution and the interquartile interval for nonparametric distribution. The significance of differences between the 2 parameters was assessed using the Mann-Withney and x2 tests. Differences were considered statistically significant at p = 0.05.
In patients of the main group with the severity of the condition according to SAPS II<30 баллов применение L-орнитин-L-аспартата (Гепа-Мерц) в комплексе лечения привело к более быстрому восстановлению нервно-психической сферы, что оценивалось в ТСЧ. При поступлении у пациентов обеих групп длительность счета была выше нормы (норма - не более 40 с) на 57,4% в основной группе и на 55,1% - в контрольной: соответственно 94 с (80; 98) и 89,5 с (58,5; 116). На фоне терапии отмечалась положительная динамика в обеих группах. На 3-й сутки длительность счета составила 74 с (68; 78) в основной группе и 82,3 с (52,5; 100,5) - в группе сравнения, что превышало норму на 45,9 и 51,2% соответственно (р=0,457, Mann-Withney). На 5-е сутки время в ТСТ составило 50 с (48; 54) в основной группе и 72,9 с (44; 92) - в контрольной, что превышало норму на 20 и 45,2% соответственно (р=0,256, Mann-Withney). Статистически достоверные изменения отмечены на 15-е сутки исследования: в основной группе - 41 с (35; 49), что превышало нормальное значение на 2,4%, а в контрольной — 61 с (41; 76) (больше нормы на 34,4%; р=0,038, Mann-Withney) - рисунок "Динамика состояния нервно-психической сферы у больных с суммарным баллом по SAPS II <30".
In patients with SAPS II severity> 30 points, the study revealed a positive effect of L-ornithine-L-aspartate (Hepa-Merz) on the dynamics of biochemical parameters; the most significant changes concerned the indicators of cytolytic syndrome (ALT, ACT) and the rate of recovery of neuropsychic functions.
Dynamic observation of the severity of the patient's condition, assessed by the SOFA scale, also showed a more rapid normalization in the main group (Figure "Dynamics of the severity of the condition in patients with a total SAPS II score> 30"). The severity of the condition of patients in the main and control groups on the 1st day of the study on the SOFA scale was 4 (3; 6.7) and 4.2 (2; 7) points, respectively, on the 3rd day of the study - 2 (1; 3 , 7) and 2.9 (1; 4) points (p = 0.456, Mann-Withney), on the 5th day - 1 (0; 2) and 1.4 (0; 2) points, respectively (p = 0.179 , Mann-Withney), on the 15th day: in the main group on average 0 (0; 1) points, in 13 (11%) patients - 1 point; in the control group, signs of organ dysfunction were observed in 12 (34%) patients, the average SOFA value in this group was 0.9 (0; 2) points (p = 0.028, Mann-Withney).
The use of L-ornithine-L-aspartate (Hepa-Merz) in our study was accompanied by a more pronounced decrease in cytolysis indices than in the control (Figures "Dynamics of ALT content in patients with a total SAPS II score> 30" and "Dynamics of ACT content in patients with a total SAPS II score> 30 ").
On the 1st day, ALT and ACT levels exceeded the upper limit of the norm in all patients. The average ALT content in the main group was 137 U / L (27.5; 173.5), in the control group - 134.2 U / L (27.5; 173.5), ACT - respectively 120.5 U / L ( 22.8; 99) and 97.9 U / l (22.8; 99). On the 3rd day, the ALT content was, respectively, 83 U / L (25; 153.5) and 126.6 U / L (25; 153.5) (p-0.021, Mann-Withney), ACT - 81.5 U / l (37; 127) and 104.4 U / l (37; 127) (p = 0.014, Mann-Withney). On the 5th day, the average ALT content in the main and control groups was 62 U / L (22.5; 103) and 79.7 U / L (22.5; 103), respectively (p = 0.079, Mann-Withney), a ACT - 58 U / L (38.8; 80.3) and 71.6 U / L (38.8; 80.3) (p = 0.068, Mann-Withney). The concentration of ALT and ACT in patients receiving L-ornithine-L-aspartate (Hepa-Merz) reached normal values on the 15th day. The ALT level in the main group was 38 U / L (22.5; 49), in the comparison group - 62 U / L (22.5; 49) (p = 0.007, Mann-Withney), the ACT level was 31.5, respectively. U / L (25; 54) and 54.2 U / L (25; 70) (p = 0.004, Mann-Withney).
The study of attention using HST in patients with a severity of the SAPS II condition> 30 points also revealed the best results in the main group (Figure "Dynamics of the state of the neuropsychic sphere in patients with a total SAPS II score> 30").
The counting rate by the 3rd day was higher than in the comparison group by 18.8%: 89 s (69.3; 105) and 109.6 s (90; 137) were spent, respectively (p = 0.163, Mann -Withney); by the 5th day, the difference reached 34.7%: 59 s (52; 80) and 90.3 s (66.5; 118), respectively (p = 0.054, Mann-Withney). On the 15th day in the main group, the account took an average of 49 s (41.5; 57), which was 47.1% more than in the control group: 92.6 s (60; 120); p = 0.002, Mann-Withney.
The immediate results of treatment should also include a decrease in hospitalization time by an average of 18.5% in patients of the main group (p = 0.049, Mann-Withney).
In the control group, there were 2 (6%) deaths from increasing multiple organ failure (p = 0.15; Χ 2), in the main group there were no deaths.
Observation showed that in the vast majority of cases, L-ornithine-L-aspartate (Hepa-Merz) was well tolerated by patients. In 7 (3.8%) patients, side effects were noted, in 2 (1.1%) the drug was canceled due to the development of an allergic reaction, in 5 (2.7%) there were dyspeptic symptoms in the form of nausea, vomiting, which were stopped with a decrease in the rate of administration of the drug.
Timely use of L-ornithine-L-aspartate (Hepa-Merz) in the complex of therapeutic measures for acute pancreatitis is pathogenetically justified and can significantly reduce the severity of endogenous intoxication. L-ornithine-L-aspartate (Hepa-Merz) is well tolerated by patients.
Literature
1. Bueverov A.O. Hepatic encephalopathy as the main manifestation of liver failure // Materials of the satellite symposium of the Merz company "Liver diseases and hepatic encephalopathy", April 18, 2004, Moscow. - S. 8.
2. Ivanov Yu.V. Modern aspects of the onset of functional liver failure in acute pancreatitis // Mathematical morphology: electronic mathematical and biomedical journal. -1999; 3 (2): 185-195.
3. Ivashkin V.T., Nadinskaya M.Yu., Bueverov A.O. Hepatic encephalopathy and methods of its metabolic correction // RMZh Library. - 2001; 3 (1): 25-27.
4. Laptev V.V., Nesterenko Yu.A., Mikhailusov S.V. Diagnostics and treatment of destructive pancreatitis - M .: Binom, 2004 .-- 304 p.
5. Nadinskaya M.Yu., Podymova S.D. Treatment of hepatic encephalopathy with Hepa-Merz // Materials of the satellite symposium of the Merz company "Liver diseases and hepatic encephalopathy", April 18, 2004, Moscow. - S. 12.
6. Ostapenko Yu.N., Evdokimov E.A., Boyko A.N. Experience of conducting a multicenter study in a medical institution in Moscow to study the effectiveness of using Hepa-Merz for endotoxicosis of various etiologies // Materials of the second scientific-practical conference, June 2004, Moscow. - S. 31-32.
7. Popov T.V., Glushko A.V., Yakovleva I.I. and others. Experience of using the drug Selenase in the complex of intensive care of patients with destructive pancreatitis // Consilium Medicum, Infections in surgery. - 2008; 6 (1): 54-56.
8. Saveliev B.C., Filimonov M.I., Gelfand B.R. et al. Acute pancreatitis as a problem of urgent surgery and intensive care // Consilium Medicum. - 2000; 2 (9): 367-373.
9. Spiridonova E.A., Ulyanova Y.S., Sokolov Yu.V. The use of Hepa-Merz preparations in the complex therapy of fulminant viral hepatitis // Materials of the satellite symposium of the Merz company "Liver diseases and hepatic encephalopathy", April 18, 2004, Moscow. - S. 19.
10. Kircheis G. Therapeutic efficacy of L-ornithine-L-aspartate infusions in patients with cirrosis and hepatic encephalopathy: results of placebo-controlled, double-blind study // Hepatology. - 1997; 1351-1360.
11. Nekam K. et al. Effect of in vivo treatment with ornitin-aspartate hepamerz on the activity and expression of superoxidedismutase SOD in patients with cirrhosis of the liver // Hepatology. -1991; 11: 75-81.
Like the medical article, news, lecture on medicine from the category
« / / / »:
Rp: Sol. Ornithini aspartat 5,0 - 10 ml
D.t.d.N. 5 in amp.
S. According to the scheme.
pharmachologic effect
Hypoammonaemic remedy. Reduces elevated levels of ammonia in the body, in particular in liver diseases. The action is associated with the participation of Krebs in the ornithine cycle of urea formation (the formation of urea from ammonia). Promotes the production of insulin and growth hormone. Improves protein metabolism in diseases requiring parenteral nutrition.
Ornithine aspartate in the body dissociates into the amino acids ornithine and aspartate, which are absorbed in the small intestine by active transport through the intestinal epithelium. It is excreted in the urine.
Mode of application
For adults: Inside. Dissolve the contents of 1-2 packages of Hepa-Merz in a large amount of liquid (in particular a glass of water or juice) and take it during or after meals up to 3 times a day.
I / v. The dosage is often up to 4 ampoules (40 ml) per day. In case of precoma or coma, inject up to 8 ampoules (80 ml) within 24 hours, depending on the severity of the condition. Before the introduction, add the contents of the ampoule to 500 ml of solution, but do not dissolve more than 6 ampoules in 500 ml of infusion solution.
The highest rate of administration of L-ornithine-L-aspartate is 5 g / h (which corresponds to the contents of 1 ampoule).
The period of treatment with Hepa-Merz is determined by the doctor depending on the clinical condition of the patient.
Indications
Treatment of patients with concomitant diseases and complications caused by impaired liver detoxification function (in particular, with liver cirrhosis) with symptoms of latent or severe hepatic encephalopathy
- especially disturbances of consciousness (precoma, coma).
Contraindications
Acute and chronic liver diseases accompanied by hyperammonemia. Hepatic encephalopathy.
- For the dynamic study of the function of the pituitary gland.
- As a corrective additive to parenteral nutrition drugs in patients with protein deficiency.
- Severe renal dysfunction (serum creatinine content more than 3 mg / 100 ml).
- If nausea or vomiting occurs, the rate of administration should be optimized.
- When using a certain dosage form of ornithine, compliance with specific indications should be observed.
- Influence on the ability to drive vehicles and control mechanisms
- Ornithine can cause disturbances in concentration and psychomotor speed.
Side effects
From the gastrointestinal tract: rarely (> 1/10 000,<1/1000) — тошнота, рвота, боль в желудке, метеоризм, диарея.
- on the part of the musculoskeletal system: very rarely (<1/10 000) — боль в суставах.
- These side reactions are often short-lived and do not require discontinuation of the medication. They disappear when the dosage or the rate of administration of the drug is reduced.
- Allergic reactions are possible.
Release form
Gran. 3 g / 5 g 5 g bag, No. 30, No. 50, No. 100
Ornithine aspartate 3 g / 5 g.
Other ingredients: anhydrous citric acid, sodium saccharin, sodium cyclamate, povidone 25, fructose, lemon flavor, orange flavor, yellow-orange dye S (E110).
Conc. d / r-ra d / inf. 5 g amp. 10 ml, No. 10
Ornithine aspartate 0.5 g / ml.
Other ingredients: water for injection.
ATTENTION!
The information on the page you are viewing was created for informational purposes only and does not in any way promote self-medication. The resource is intended to familiarize healthcare workers with additional information about certain medications, thereby increasing their level of professionalism. Use of the drug " Ornithine aspartate"without fail provides for a consultation with a specialist, as well as his recommendations on the method of application and dosage of the medicine you have chosen.
Gross formula
C 5 H 12 N 2 O 2Pharmacological group of substance Ornithine
Nosological classification (ICD-10)
CAS code
70-26-8Characteristics of the substance Ornithine
Colorless crystals. Let's easily dissolve in water, alcohol, it is difficult to dissolve in ether.
Pharmacology
pharmachologic effect- hepatoprotective, detoxification, hypoazotemic.It has a hypoammonoic effect. Utilizes ammonium groups in the synthesis of urea (ornithine cycle). Reduces the concentration of ammonia in the blood plasma, helps to normalize the body's acid base and the production of insulin and growth hormone. Improves protein metabolism in diseases requiring parenteral nutrition.
When taken orally, ornithine aspartate dissociates into its constituent components (ornithine and aspartate), which are absorbed in the small intestine by active transport through the intestinal epithelium.
It is excreted in the urine through the urea cycle.
Application of the substance Ornithine
Hyperammonemia, hepatitis, liver cirrhosis, hepatic encephalopathy (latent and severe), incl. as part of complex therapy for impaired consciousness (precoma or coma); as a corrective supplement to parenteral nutrition drugs in patients with protein deficiency.
Contraindications
Hypersensitivity, severe renal failure (creatinine concentration more than 3 mg / 100 ml).
Application during pregnancy and lactation
During pregnancy, it is possible only under the strict supervision of a doctor. During treatment, breastfeeding should be discontinued.
Side effects of the substance Ornithine
Allergic skin reactions, nausea, vomiting.
Interaction
Pharmaceutically incompatible with penicillin, vitamin K, rifampicin, meprobamate, diazepam, phenobarbital, ethionamide.
Route of administration
Inside, i / v, i / m.
Precautions for the substance Ornithine
Use with caution to vehicle drivers and people whose work requires a quick mental and physical reaction, and is also associated with increased concentration.
If nausea or vomiting occurs, the rate of administration of the drug should be reduced.
Interaction with other active ingredients
Trade names
| Name | The value of the Vyshkovsky Index ® |
Summary
The work presents the pathogenesis of liver failure. The data on the treatment of patients with liver cirrhosis of various etiology complicated by hepatic encephalopathy are presented. A large number of different tests and biochemical parameters have shown the positive role of L-ornithine-L-aspartate (Ornitox) in stabilizing the patient's condition, reducing the clinical manifestations of the disease, and normalizing biochemical parameters.
Keywords
Ammonia, liver failure, ways of correction, Ornitox, Glutargin.
Ammonia is the end product of nitrogen metabolism in the human body. It is formed during the metabolism of proteins, amino acids and other nitrogenous compounds. It is highly toxic to the body, and most of it during the ornithine cycle is converted by the liver to the less toxic compound carbamide (urea) and excreted by the kidneys.
Simultaneously, ammonia is involved in the resynthesis of amino acids and keto analogs of amino acids, and this process is called "reductive amination".
In a healthy body, a certain balance of ammonia is constantly maintained, and the main sources of its formation are:
- large intestine (processing of protein and urea by the bacterial flora);
- musculature (in proportion to physical activity);
- small intestine (breakdown of the amino acid glutamine - the main source of energy for the cells of the intestinal mucosa);
- liver (protein breakdown).
With various diseases leading to impaired ammonia metabolism (most often this occurs with impaired liver function - hepatitis, cirrhosis), the level of this chemically active substance becomes one of the main reasons for the development of severe endotoxicosis.
The pathological symptoms arising in acute or chronic hepatic encephalopathy are based on the hypothesis that endogenous neurotoxins and amino acid imbalances resulting from hepatocyte insufficiency and / or portosystemic shunting of blood lead to edema and functional disorders of astroglia.
The leading role in this process belongs to ammonia, mercoptans, short- and medium-chain fatty acids, phenols. Their toxic effect leads to disruption of the permeability of the blood-brain barrier, disruption of the functions of ion channels and neurotransmission, and as a result, the supply of neurons with high-energy compounds decreases.
The role in this process of increasing the content of GABA (gamma-aminobutyric acid), an important inhibitory mediator, is also undoubted. As a result of liver damage, the level of activity of GABA transaminase, which plays an important role in the elimination of excess GABA content, decreases, which aggravates the course of encephalopathy.
In recent years, the main reason for the development of liver failure is the glia hypothesis, which links two levels: the liver - the brain. According to this hypothesis, hepatocellular failure leads to amino acid imbalance and ammonia accumulation, that is, ammonia endotoxicosis occurs. Hyperammonemia in liver diseases is associated with a decrease in urea and glutamine in it. Ammonium compounds (ammonia) in non-ionized form penetrate the blood-brain barrier, involving aromatic amino acids in this process, as a result of which the synthesis of false neurotransmitters and serotonin is enhanced.
Thus, hepatic encephalopathy is a neuropsychiatric syndrome with impaired intelligence, consciousness, neurological disorders, which develops in patients with acute or chronic hepatic failure against the background of various liver lesions. In accordance with these manifestations, several variants of this syndrome are distinguished. In addition to the signs shown in table. 1 use a variety of psychometric tests.
Regardless of the causes of liver failure, in the treatment of this disease, an important role is played by a diet with limited protein, drugs that affect the main links of pathogenesis, in particular, the use of universal cytoprotectors - cytoflavin, reamberin, that is, substances that reduce toxic-hypoxic damage to neurons and restoring their energy reserves, and drugs aimed at stopping hyperammonemia.
These include lactulose, a synthetic disaccharide that reduces the concentration of ammonia in the blood by reducing its intake from the intestine; to reduce the formation of toxins, including ammonia, antibiotics such as vancomycin, ciprofloxacin, nitronidazole, and branched-chain amino acid preparations are sometimes used. Zinc can also be used as an adjunctive therapy.
In recent years, the most promising for the disposal of ammonia is the appointment of drugs based on L-ornithine-L-aspartate. L-ornithine activates ornithinecarbamoyltransferase and carbamoylphosphate synthetase in the periportal hepatocytes - the first enzyme of the urea synthesis cycle.
L-ornithine and L-aspartate are substrates for the synthesis cycle of both urea and glutamine. The glutamine synthetase reaction is activated by the action of L-ornithine-L-aspartate not only in the liver, but also in the muscles.
It is also important that aspartate is incorporated into the Krebs cycle, that is, it increases the synthesis of macroergs and reduces the formation of lactic acid, which, in turn, reduces the BBB permeability for toxic substances.
Here are its main pharmacological properties.
L-Ornithine-L-Aspartate (Ornitox) has a dual mechanism by incorporating both amino acids into the ornithine cycle.
L-ornithine:
- is included in the urea cycle as a substrate (at the stage of citrulline synthesis);
- is a stimulant of carbamoyl phosphate synthetase I (the first enzyme of the urea cycle);
- is an activator of the glutamine synthetase reaction in the liver and muscles, reduces the concentration of ammonia in the blood plasma;
- helps to normalize the acid-base balance of the body;
- promotes the production of insulin and growth hormone;
- improves protein metabolism in diseases requiring parenteral nutrition.
L-aspartate:
- is included in the urea cycle at the stage of arginine succinate synthesis;
- is a substrate for the synthesis of glutamine;
- participates in the binding of ammonia in perivenous blood, hepatocytes, brain, and other tissues;
- stimulates the synthesis of glutamine in muscles and perivenous hepatocytes;
- has a stimulating effect on inactive or affected liver cells;
- stimulates regeneration, improves energy processes in damaged liver tissue;
- participates in the tricarboxylic acid cycle;
- has the ability to penetrate cell membranes by active transport;
- inside the cell, it participates in the processes of energy metabolism in mitochondria, thereby increasing the energy supply of the tissue;
- has an anabolic effect on muscles.
The second most important drug in the treatment of this pathology is the drug Glutargin (arginine glutamate), which has also shown its sufficient effectiveness in clinical practice. And when it was created and appeared in the clinic (more than 10 years ago), arginine glutamate was a kind of "magic wand".
At the same time, certain side effects of this drug are possible. These include:
- changes in the balance of intracellular potassium;
- hyperthermia, shortness of breath, the appearance of pain behind the sternum - these episodes most often occur after a rapid intravenous injection of the drug;
- heart rhythm disturbances in the form of atrial fibrillation (restriction of administration in patients with rhythm disturbances);
- headache, dizziness, tremor, general weakness (which, against the background of encephalopathy, creates certain diagnostic difficulties).
These effects are associated with the mechanism of action of glutamic acid, which is part of arginine glutamate, which belongs to the class of excitatory amino acids, therefore, the binding of glutamate to specific receptors of neurons leads to their excitation. In some cases, this can lead to overexcitation of neurons and their death.
It should be noted that these effects of the drug do not detract from the merits of arginine glutamate, but may limit its use.
The aim of the study was to determine the efficacy and safety of complex therapy in patients with hepatic encephalopathy of various origins, II-III degree.
Materials and methods
45 patients with liver cirrhosis of various origins, diagnosed with liver failure, were examined. The average age of the patients was 50.1 ± 6.8 years, men predominated among the examined - 72.0%. The duration of the disease was 3.5 ± 1.5 years, the cause of the disease in 66.4% of cases was alcohol abuse, 15.6% had liver damage of mixed genesis, and 18.0% had viral etiology.
When assessing the objective status, dyspeptic syndrome was diagnosed in 100% of patients, painful - in 78%, icteric - in 67%, edematous-ascitic - in 82%, cytolytic syndrome - in 82%, hypersplenism - in 74%.
The patients were divided into three equal groups.
The first (main) received Reamberin, Cyto-flavin, Lactulose, detoxification therapy and L-ornithine-L-aspartate (Ornitox) intravenously.
The second (control) group received essential phospholipids instead of L-ornithine-L-aspartate (Ornitox).
The third group (comparison group) received arginine glutamate (Glutargin) at a dose of 6 g per day by intravenous drip, the rate of administration is 60 drops per minute.
Assessment of the condition and biochemical studies were carried out on the day of admission and 10 days after the start of treatment.
The average dose of L-ornithine-L-aspartate (Ornitox) was 10 g, which were injected intravenously per 400 ml of saline. The rate of administration is 8-12 drops per minute. The duration of therapy was 10 days. In the future, patients were recommended oral administration of the drug.
Signs of hepatic encephalopathy were exhibited in all examined patients and are presented in table. 2.
Results and its discussion
Assessment of the general condition of patients 10 days after the start of treatment showed a positive trend in patients of all groups, but in the main group a significant improvement was found already by the 5th day from the start of treatment. These positive changes were more pronounced by the 10th day of stay in the clinic (Tables 3, 4). Positive, but less significant changes were noted in patients in the comparison group.
Similar data were obtained when studying the levels of enzyme and bilirubin, ammonia.
The revealed positive shifts in the homeostasis of the examined patients, especially in the patients of the main group, also correlated with a decrease in the clinical manifestations of the symptoms of hepatic encephalopathy. This improvement was more pronounced in patients in the Ornitox group (Table 5).
A pronounced positive dynamics in the form of a decrease in the symptoms of hepatic encephalopathy in patients of the main group correlated with a decrease in ALT, AST, total bilirubin, and ammonia content.
Comparative analysis of clinical and biochemical parameters in patients of the main group and the comparison group showed certain advantages of using L-ornithine-L-aspartate (Ornitox) in comparison with other drugs, in particular with arginine glutamate (Glutargin). This is especially true for a decrease in the level of ammonia, urea, alkaline phosphatase in patients of the main group. Obviously, this is due to the fact that L-ornithine-L-aspartate is involved in biochemical cycles at earlier stages of disturbed metabolic processes, as well as due to the incorporation of both amino acids into the ornithine cycle, which contributes to a more efficient neutralization (utilization) of ammonia and, as a consequence, - more effective improvement of the clinical picture of the disease.
Thus, the results obtained, the mechanism of action of L-ornithine-L-aspartate (Ornitox) indicate the advisability of including this drug in the treatment of patients with hepatic insufficiency, especially complicated by hepatic encephalopathy. Based on the fact that the violation of ammonia metabolism occurs immediately with liver damage, it is obvious that L-ornithine-L-aspartate - (Ornitox) should be included in therapy in the early stages of the disease. The duration of treatment depends on many reasons and may continue, in our opinion, for a long time. The use of higher doses of the drug is advisable in patients with acute liver failure.
With long-term administration of Ornithox in sufficiently large doses, we did not observe side or undesirable effects, which indicated the safety of this drug.
And in conclusion, it should be noted that the obtained positive results of the use of this drug were obtained in patients with stage II-III of hepatic failure against the background of the use of universal cytoprotectors, which improve the function of not only hepatocytes, but also neurons.
Bibliography
1. Golubovskaya O.A., Shkurba A.V. The effectiveness of Ornithox in the complex treatment of fulminant hepatic failure in the clinic of infectious diseases // Suchasni Infections. - 2010. - No. 2. - S. 10-13.
2. Kondratenko P.G., Smirnov N.L. L-ornithine-L-aspartate in the treatment of patients with urgent surgical abdominal pathology // Surgery. - 2010. - No. 3. - S. 112-115.
3. Shipulin V.P., Chernyavsky V.V. Toxic hepatitis: how to increase the effectiveness of treatment // News of Medicine and Pharmacy. - 2010. - No. 348. - S. 25-29.
4. Samogalskaya O.E. The effectiveness of the use of thio-cetam in the treatment of liver failure // International neurological journal. - 2006. - No. 3 (70). - S. 48-53.
5. Babak O.Ya., Kolesnikova E.V., Kozyrev T.E. Modern possibilities of correction of hepatic encephalopathy in patients with liver cirrhosis // Suchasna gastroenterology. - 2010. - No. 4 (54). - S. 38-43.
Pharmacological group: Hypoammonaemic drugs;
Pharmacological action: Hypoammonaemic drug. Reduces elevated levels of ammonia in the body, in particular, in liver diseases. The action of the drug is associated with its participation in the ornithine cycle of Krebs urea formation (the formation of urea from ammonia). Promotes the production of somatotropic hormone. Improves protein metabolism in diseases requiring parenteral nutrition.
Ornithine is an amino acid that plays an important role in the urea cycle. When ornithine carbamoyltransferase is deficient, there may be an abnormal accumulation of ornithine in the body. Ornithine is one of three amino acids that are involved in the ornithine cycle (together with and). Taking these amino acids lowers the level of ammonia, which, according to preliminary data, increases the level of performance.
reference
L-Ornithine is a non-protein amino acid (not involved in protein production) that is involved in the ornithine cycle, and the entry of ornithine into the cell is the rate-limiting step of the cycle. Ornithine bonds with a molecule known as carbamoyl phosphate, which requires ammonia to appear, and these are then converted to L-citrulline to form urea. It is the conversion stage that reduces the level of ammonia in the blood and, in parallel, increases the level of urea. It is assumed that L-ornithine plays an important role in those conditions of the body that are characterized by excessive levels of ammonia - mainly hepatic encephalopathy (clinical liver disease) and prolonged cardio training. In people suffering from hepatic encephalopathy, there is a decrease in serum ammonia levels (in most studies, the drug was administered by infusion, although a similar effect was achieved through oral administration of high doses), while there were only two studies evaluating the effect of the drug during cardio training. In the one that was better suited for assessing the effects of ammonia (prolonged training instead of vigorous training), ornithine was found to reduce fatigue. In addition, a reduction in fatigue has been reported by both people suffering from hepatic encephalopathy and those suffering from a hangover (excessive alcohol consumption increases serum ammonia levels) if they took ornithine before alcohol use. To date, only one study has been conducted on the combined effects of ornithine and arginine, during which there was an increase in lean tissue mass and strength output of weightlifters, but this study has been conducted for a long time and has not been repeated since, and its practical significance is unclear. Finally, the effect of ornithine on increasing growth hormone production is similar to that of arginine. However, although technically this effect does occur, it does not last too long, and the body compensates for all the changes in a day, so that such an effect of growth hormone is not significant. Based on the fact that the main characteristics of growth hormone (an increase in the mass of non-adipose tissue and the burning of fat) act for a whole day, and not instantly, ornithine simply does not have time to have any significant effect on the body. In conclusion, it should be noted that ornithine has some potential due to its ability to lower the concentration of ammonia in the blood, thereby increasing the power output during prolonged training (45 minutes or more), which is partly due to the fact that the drug remains in the blood for several hours after administration. , even in spite of physical activity. Other names: L-ornithine Notes:
Arginine is known to cause diarrhea at a dosage of 10 g or more, and since ornithine uses the same intestinal pathogens (which, when absorbed into the intestines, cause diarrhea), it is likely that ornithine can reduce the dosage of arginine required for diarrhea.
Ornithine, at high dosages of 10-20g, can cause diarrhea on its own, but less likely than from exposure to arginine.
Variety:
Amino acid dietary supplements
Pairs well with:
Anionic salts such as alpha ketoglutarate
Works best in the following situations:
Fatigue and stress (chronic)
Hepa-Merz: instructions for use
Ornithine (in the form of hydrochloride) is taken daily at 2-6 g. Nearly all studies are conducted within this standard dosage, however, although serum levels are only slightly dose-dependent, dosages above 10g can cause intestinal distress. Most studies use Ornithine HCl, which has been shown to be effective. Ornithine hydrochloride is, by weight, 78% ornithine, therefore, for a dosage ranging from 2 to 6g, the equivalent dosage of L-ornithine-L-aspartate (50%) would be 3.12-9.36g, and the equivalent dosage of L-ornithine α- ketoglutarate (47%) will be 3.3-10g. In theory, these two varieties are more effective, but there is a lack of adequate comparative data.
Origin and meaning
Origin
L-Ornithine is one of three amino acids that are involved in the ornithine cycle and is similar to the other, L-citrulline, but not L-arginine. L-ornithine is a non-protein amino acid that is not involved in the formation of enzymes and protein structures, and also does not have its own genetic code and does not carry any nutritional value. Dietary L-arginine is a conditionally essential amino acid that circulates L-ornithine and L-citrulline in the blood (glutamate and glutamine may also participate in this) in order to maintain the required level of circulating L-ornithine concentration in the blood at about 50 μmole / ml. L-ornithine can also be formed directly from L-arginine using the enzyme arginase (as a result of which urea is formed). L-Ornithine is a non-protein amino acid that is formed from other amino acids, the most famous of which are also involved in the ornithine cycle - L-arginine and L-citrulline
Metabolism
Ornithine does not participate in the nitric oxide cycle, but rather is an intermediate product after the release of urea, which combines with ammonia (via carbamoyl phosphate) to subsequently form citrulline. The ornithine cycle involves 5 enzymes and three amino acids (arginine, ornithine and citrulline) and one intermediate, which regulates the concentration of urea and ammonia in the body. Sometimes this cycle is viewed as the production of nitric oxide (since it prevents an increase in the toxic concentration of ammonia, a compound with a low nitrogen content), and the participation of ornithine limits the rate of this reaction. L-arginine is converted to L-ornithine by the enzyme arginase (resulting in the release of urea) and subsequently ornithine (using carbamoyl phosphate as a cofactor) promotes the production of L-citrulline by the enzyme ornithine carbamoyl transferase. In this sense, the metabolic pathway from arginine to citrulline (via ornithine) causes an increase in urea and a parallel decrease in ammonia levels, which helps carbamoyl phosphate synthase to produce carbamoyl phosphate, and a lack of this enzyme leads to high levels of ammonia in the blood, which is probably the largest genetic deficiency in the ornithine cycle. If needed, arginine can be directly converted to L-citrulline by increasing the ammonia concentration using the enzyme arginine deiminase. The cycle begins with citrulline, then interacts with L-aspartate (the isomer of which is D-aspartic acid) and, with the help of the enzyme argininosuccinate synthetase, argininosuccinate is formed. As a result, the enzyme argininosuccinate lyase cleaves argininosuccinate into free arginine and fumarate. Then arginine is re-incorporated into the ornithine cycle. Furmarat can simply be included in the Krebs cycle as an energy intermediate. Ornithine, citrulline and arginine are involved in the ornithine cycle, which can replace each other to regulate the concentration of ammonia in the blood. spermidine and spermine. Ornithine is a precursor for the formation of polyamine compounds. L-ornithine can be converted to a metabolite known as l-glutamyl-c-semialdehyde, which can be further converted to the neurotransmitter glutamate by P5C dehydrogenase. Pyrroline-5-carbroxylate is involved in this potentially reversible process as an intermediate. The amino acids of the ornithine cycle are also partially related to neurology, since ornithine can be converted to glutamate (which, in turn, can be converted to GABA, which is very important for neurology).
Pharmacology of ornithine
Absorption
Ornithine moves through the body in the same way as L-arginine (and L-cysteine), but not in the same way as L-citrulline. Ornithine is absorbed in the same way as arginine. Although the data obtained in the study of oral digestibility of ornithine are not as detailed as in a similar study of arginine, there is reason to believe that they are characterized by uniform amino acid sequences (good bioavailability at low oral dosages from 2 to 6 g, and with a systematic decrease and increase dosage, assimilation is becoming less and less effective).
Blood serum
40-170mg / kg of ornithine taken orally (for a person weighing 70kg, this is 3-12g) can, within 45 minutes and, depending on the dosage, increase the level of ornithine in the blood serum (although it is not precisely established how much), which will remain unchanged in over the next 90 minutes. One study noted that 100mg / kg of the drug raised serum ornithine levels from about 50μmol / ml to 300μmol / ml within an hour, which affected the body as a grueling 15-minute workout followed by 15-minute rest. In another study, subjects were injected with 3 g of ornithine in the morning and another dose 2 hours later, and it was found that even after 340 minutes, the level of ornithine in the blood plasma was 65.8% higher than the placebo effect, although this figure had already begun to decline (after 240 minutes the level ornithine was more by 314%). Ornithine is quite well absorbed and its effect peaks 45 minutes after oral administration (or slightly earlier) and remains at this level for 4 hours (somewhere between 4 and 6 hours the decline begins). It was noted that taking 2000 mg of ornithine does not increase serum citrulline and arginine levels - neither by itself, nor by interaction with hydrochloride, and only ornithine in ornithine-α-ketoglutarate (a special food compound) can increase plasma arginine levels ... Taking ornithine (100mg / kg in conjunction with hydrochloride) before a grueling workout increased plasma glutamate levels, both during rest and after the workout itself (although not much - to about 50μmol / ml, or 9%). In one study, there was a transient 4.4-9% increase in the activity of three BCAAs after four hours of grueling exercise, before which subjects took 6g of ornithine (two doses of 3g after two hours). After grueling exercise, there may be a slight increase in glutamate levels, and small doses of ornithine have little or no effect on blood levels of arginine or citrulline.
Ornithine in bodybuilding
The mechanism of action of the drug
The accumulation of ammonia in skeletal muscle can provoke muscle fatigue when protein-induced muscle contractility is inhibited. During exercise, ammonia usually builds up in the blood serum and in the brain, and it builds up in the brain and causes fatigue. It has been found that after taking 100mg / kg of L-ornithine, ammonia levels can rise after a grueling exercise of about 15 minutes, while no such effect is observed at rest. With longer training sessions (within 2 hours at 80% VO2max), the rise in serum ammonia begins to decrease. Skeletal muscles are able to independently increase the level of ammonia (through alanine and glutamine), and the ammonia itself, reaching the liver, can be converted into urea. However, taking 100mg / kg of ornithine does not seem to have any effect on urea levels during a grueling workout of about 15 minutes. However, after two hours of cycling and exposure to ornithine (2g daily and 6g daily), urea levels still increased compared to placebo, which is probably due to a decrease in the amount of drug administered before the test (in in the placebo group, the drug content was reduced by 8.9%, in the test group - no change). Although taking ornithine has a positive effect on the ornithine cycle, ornithine has almost no effect on serum urea concentration.
Human tests
A study was conducted using 1g and 2g dosages of L-ornithine along with the same amount of L-arginine (up to 2g and 4g) and it was noted that within 5 weeks, adult men who underwent strength training gained lean mass, and showed an increase in strength. The study has shown gains in muscle mass, but the data are too limited to draw any conclusions. In addition, the drug has been tested in conjunction with arginine. The exercise test after taking 100mg / kg L-ornithine hydrochloride showed no significant effect of ornithine on physical performance (time to exhaustion, heart rate, oxygen consumption) during the entire test, which lasted about 15 minutes. In a longer 2-hour trial (at 80% VO2max), conducted after taking 2g of ornithine daily for 6 days and 6g of the drug before starting, it was noted that ornithine was 52% more effective in suppressing fatigue than placebo. Similar indicators were obtained during the 10-second sprint (with equal indicators at the start, ornithine was again more effective than placebo), but neither ornithine nor placebo had any effect on average speed. It appears that ornithine can only prevent fatigue during prolonged exercise, which roughly coincides with the onset of ammonia complications. Notwithstanding the above, too few studies have been conducted to draw concrete conclusions.
Effects on the body
5interactions with organ systems
Liver
Hepatic encephalopathy is a condition of the liver (which affects 84% of people with cirrhosis of the liver) that, due to the high concentration of ammonia in the blood and brain, negatively affects cognitive functioning. In a sense, this condition can be called toxic effects of ammonia. Treatment for hepatic encephalopathy is usually based on a decrease in the concentration of ammonia in the blood. Intravenous infusion of L-ornithine can reduce the circulating concentration of ammonia in a clinical setting, while oral administration of L-ornithine-L-aspartate three times a day, 6 g (total 18 g) for 14 days, effectively lowers the level of ammonia in the blood, regardless of intake food. The reviews on this topic (one of them looked at 4 trials and a meta-analysis) are quite promising, but limited by the scale of the studies, and their merits may be limited to observing encephalopathy, instead of looking for a way to combat it. Hepatic encephalopathy is a liver condition characterized by high concentrations of ammonia in the blood and brain, which have cognitive side effects. Taking ornithine can lower the concentration of ammonia in the blood of people in whom encephalopathy accompanies liver cirrhosis, but data on specific oral dosages are too limited (most studies were carried out by intravenous administration of the drug in a clinical setting).
6interactions with hormones
A growth hormone
It was noted that after the administration of ornithine, the concentration of growth hormone circulating in the blood increases, which depends on the hypothalamus. A daily intake of 2,200mg of ornithine, along with 3,000mg of arginine and 12mg of B12 for three weeks, can increase the concentration of growth hormone in blood plasma by 35.7% (measured immediately after training) and, although the concentration began to decrease within an hour, it still remained higher than those in the placebo group. A trial was conducted on 12 bodybuilders, during which they were injected with large doses of 40, 100 or 170 mg / kg of ornithine hydrochloride and it was noted that only the highest dosage (170 mg / kg, or 12 g per person weighing 70 kg) was able to increase the concentration of the hormone growth was 318% higher than the initial level 90 minutes after drug administration, while at 45 minutes there were no significant changes. Despite this result, the authors of the study believe that it does not really matter, since the increase occurred from 2.2 +/- 1.4 ng / ml to 9.2 +/- 3.0 ng / ml, while normal daily fluctuations in the level of growth hormone vary between zero and 16ng / ml. Ornithine administration can cause a spike in growth hormone levels. However, due to the interaction between arginine and growth hormone (namely the fact that the spike does not persist throughout the day), ornithine is only part of the whole process. These results may not be practical.
Testosterone
Parallel administration of ornithine and arginine did not significantly affect the concentration of testosterone in the blood of people who were subjected to strength training, introducing 2.200 mg of ornithine and 3.000 arginine for 3 weeks. There is no evidence of a positive effect of ornithine on testosterone levels.
Cortisol
There are various data on the effect of intravenous ornithine on cortisol levels - it is able to stimulate the adrenocorticotropic hormone and, subsequently, cortisol itself, and in another study it was found that 400 g of ornithine, administered before drinking alcohol, lowered the level of cortisol in the blood the next morning subjects (although this was more likely a consequence of the acceleration of alcohol metabolism). In addition, in a 3-week strength test, the combined effects of L-ornithine and L-arginine (2,200mg and 3,000mg, respectively) did not significantly affect cortisol levels. Ornithine has different effects on cortisol levels depending on the situation. Injections increase it (to some extent increasing the level of growth hormone, and the practical significance of the results obtained is currently not established), and, at the same time, ornithine lowers the level of cortisol, which increased as a result of alcohol intoxication. Before strength training, the drug had no effect.
Nutrient interactions
Ornithine and Alpha Ketoglutarate
Sometimes ornithine is introduced as part of the compound L-ornithine-α-ketoglutarate, which has two molecules in its composition at a stoichiometric ratio of 1: 2. These molecules (ornithine and α-ketoglutarate) are metabolically related, since ornithine can be converted to α-ketoglutarate by transformation into glutamate semialdehyde, glutamyl phosphate, glutamate, and ultimately into α-ketoglutarate. This metabolic transformation works in the opposite direction, and it is believed that the administration of α-ketoglutarate with ornithine reduces the amount of ornithine that is converted to α-ketoglutarate, instead promoting the formation of other amino acids. This was confirmed by a study in which first only ornithine (6.4 g of ornithine hydrochloride) was introduced, then α-ketoglutarate (3.6 k in the calcium salt) and, as a result, their combination (10 g of each drug), and then the latter option contributed to an increase in the level of arginine and proline (however, during all three stages, an increase in the level of glutamate was noted). Administration of ornithine together with α-ketoglutarate can suppress the conversion of ornithine to α-ketoglutarate (which occurs by default) and indirectly stimulates the formation of other amino acids such as arginine. α-ketoglutarate is also able to act as an intermediate in the metabolism of amino acids, interact with ammonia (under the influence of a reducing agent) and, as a result, form glutamine, which has a buffer effect for ammonia, independent of the ornithine cycle. Initially, it was assumed that the reducing substance would be NADH or, alternatively, formate (a product of the ornithine cycle). α-ketoglutarate is able to be an intermediate in the metabolism of glutamine, which can impart buffering properties to ammonia, by reducing glutamine, regardless of the course of the ornithine cycle.
Ornithine and Arginine
The supply of liver cells with ornithine limits the rate of ornithine synthesis and ammonia detoxification, and the introduction of L-arginine (218% at 0.36 mmol) and the D-arginine isomer (204% at 1 mmol) can stimulate the absorption of ornithine. Supplementation with arginine and / or citrulline (which provides arginine) not only increases the rate of absorption of ornithine, but can also lower blood ammonia levels. Despite the above, such actions are ineffective, and the synergism of arginine with ornithine, aimed at detoxifying ammonia, is currently not properly studied.
Ornithine and L-Aspartate
L-aspartate (not to be confused with D-aspartic acid) is commonly used with ornithine in L-ornithine-L-aspartar to treat hepatic encephalopathy. It was assumed that such an approach would be effective due to the fact that detoxification of ammonia is required for the treatment of hepatic encephalopathy, and ornithine and aspartate are both involved in the ornithine cycle (ornithine is converted to citrulline to isolate ammonia by the production of carbamoyl phosphate, and then citrulline begins to be converted to arginine with the participation of L-aspartate as a cofactor).
Ornithine and Alcohol
Due to the ability of ornithine to stimulate the ornithine cycle and accelerate the elimination of ammonia from the body, and because alcohol consumption dramatically increases ammonia levels (there is also evidence of a relationship between their metabolic pathways), it is believed that ornithine may help reduce the effects of hangovers and inebriation. Administration of 400mg L-ornithine half an hour before drinking alcohol (0.4g / kg 90 minutes before bedtime) helped to lower some of the readings taken the next morning (according to data on irritability, hostility, embarrassment, sleep duration, and fatigue from the subjects themselves) and also lower cortisol levels in people who are called "flashers" (usually Asians who do not have the gene for aldehyde dehydrogenase, which is responsible for alcohol metabolism; "flashers" are much more sensitive to alcohol than other people), but the drug did not affect the level ethanol metabolism and the state of intoxication itself. The same study refers to a previous study (which cannot be found on the web), in which 800mg of ornithine-L-aspartate was able to affect only "flashers", while the rest were not. Data are limited, but it looks like the drug may relieve hangovers in alcohol-sensitive people. Preliminary results suggest that there will be no effect on non-flashers, so the practical relevance of this information to drinkers is unknown.
Aesthetic medicine
Leather
It is assumed that L-ornithine-α-ketoglutarate (exclusively) can be used in burn therapy, since it is a precursor for both arginine and glutamine (as well as proline, but it is often not remembered). Both of these amino acids may be useful as enteral supplements in a clinical setting (arginine and glutamine, respectively). There have been several studies using L-ornithine-α-ketoglutarate given intravenously, which has accelerated the rate of recovery from burns. L-ornithine-α-ketoglutarate appears to accelerate the healing of burns in a clinical setting, but the use of L-ornithine-α-ketoglutarate as the main therapy has not been established (clinical trials do not necessarily confirm the possibility of using the drug in real conditions).
Safety and Toxicology
General information
Ornithine is spread by the same intestinal carriers as L-arginine, whereby high doses of ornithine can cause diarrhea. Since this occurs against the background of complete saturation of the carriers, the upper limit of the safe dosage (4-6 g rarely causes side effects) is the same for arginine, ornithine and other amino acids, which are distributed by the same carrier (L-cysteine). Diarrhea begins when amino acids trigger the production of nitric oxide in the gastrointestinal tract, which stimulates intestinal absorption of water and leads to osmotic diarrhea. In other studies, 20g of ornithine was administered intravenously and nasogastrically, and this also led to diarrhea. High oral doses of ornithine can also cause diarrhea, but the active dose of ornithine for diarrhea is much higher than the dose of arginine (whereas citrulline has no gastrointestinal side effects at all).
Role in the urea cycle
L-Ornithine is one of the products of the action of the enzyme arginase in the production of urea. Therefore, ornithine is a central part of the urea cycle to utilize excess nitrogen levels. Ornithine is the catalyst for this reaction. First, ammonia is converted to carbamoyl phosphate (phosphate-CONH2). Ornithine is converted to a urea derivative on delta (terminal) nitrogen using carbamoyl phosphate. Another nitrogen is added from aspartate to produce denitrogenic fumarate, and the resulting (guanidine compound) is hydrolyzed to form ornithine, producing urea. The nitrogen in urea is formed from ammonia and aspartate, while the nitrogen of ornithine remains intact.
Ornithine lactamisation
Availability:
The drug Hepa-Merz (Ornithine) is used to treat acute and chronic liver diseases accompanied by hyperammonemia; as well as hepatic encephalopathy (latent or severe). The drug is approved for use as a means of OTC.
Loading ...