EFFICACY OF L-ORNITHIN L-ASPARATE IN THE PREVENTION OF ENDOTOXICOSIS AND MITOCHONDRIAL RESPIRATORY DISFUNCTION IN ACUTE TOXIC HEPATITIS
DOI:
https://doi.org/10.11603/mcch.2410-681X.2022.i1.12683Keywords:
L-ornithine L-aspartate, endotoxicosis, mitochondrial respiration, nitric oxideAbstract
Introduction. The study of the mechanisms of action of L-ornithine L-aspartate (LOLA) in acute toxic hepatitis still remains as an actual problem. Mitochondrial respiratory disorders and endotoxicosis are known to be the leading pathogenetic causes in the mechanism of acute toxic hepatitis, as they contribute to the formation of reactive oxygen species and excessive inflammation, which can eventually lead to pathological liver remodeling.
The aim of the study – to determine the effectiveness of LOLA in preventing endotoxicosis and the impact of the drug on mitochondrial respiration in acute toxic liver disease induced by carbon tetrachloride (CCl4), and to investigate the importance of NO synthesis in these effects.
Research Methods. The study was performed on 24 white adult male rats. Acute toxic hepatitis was induced by a single intraperitoneal administration of carbon tetrachloride (2 g/kg). Corrective agents were administered for 2 days. The study was performed on the third day. LOLA was administered at a dose of 200 mg/kg of body weight, N-nitro-L-arginine methyl ester (L-NAME) – 10 mg/kg. Determination of the content of lipid hydroperoxides (LPO), ceruloplasmin (CP), medium mass molecules (MMM1 and MMM2), cytochrome oxidase activity, succinate dehydrogenase was performed according to standard methods.
Results and Discussion. In acute toxic hepatitis, the content of LPO increased by 72.64 %, MMM1 and MMM2 – by 38.32 % and 60.65 %, respectively, CP – by 31.94 %. After LOLA administration, the production of LPO was suppressed by 20.22 %, the content of MMM1 and MMM2 decreased by 16.88 % and 25 %, CP – by 14.48 %. In CCl4-induced hepatitis, the activity of cytochrome oxidase was suppressed by 25 % and succinate dehydrogenase by 23.46 %. In the group of treated LOLA rats there was an increase in the activity of these enzymes by 8.85 % and 5.42 %, respectively. Concomitant use of L-NAME inhibited all the effects of LOLA, as the content of LPO remained 31.51 % higher, MMM1 and MMM2 – 22.92 % and 37.33 % higher, CP – 15.34 % higher, while the activity of cytochrome oxidase decreased by 7.66 %, and succinate dehydrogenase activity reduced by 8.82 %.
Conclusions. LOLA prevents endotoxicosis caused by CCl4-induced hepatitis and is potentially effective in restoring mitochondrial respiration. These effects of LOLA are realized through a NO-dependent mechanism.
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