Affiliation:
1. N.P. Ogarev National Research Mordovia State University, Saransk, Russian Federation
2. I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russian Federation
3. Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russian Federation
Abstract
We studied the hepatoprotective activity of 2-aminoethanesulfonic acid derivative (laboratory code LBK-527) in antibiotic-associated liver injury. The studies were performed on 18 laboratory rats (Wistar line), divided into four groups: 1st - intact animals, 2nd - control group with tetracycline drug-induced liver injury (TDLI), 2nd group - experimental with DILI and injected LBK- 527 (28 mg/kg), group 3 – experimental with DILI, injected N-adenosyl-S-methionine for 14 days. DILI was induced by intragastric administration of tetracycline at a dose of 500 mg/kg for 5 days. Animals were removed from the experiment on 7 and 14 days and studied activity of aspartic (AST) and alanine (ALT) aminotransferases, total protein (TP), total bilirubin (TB), alkaline phosphatase (ALP), and creatinine (C). The liver was taken from all animals, weighed, and the macro- and microstructure was assessed, stained with hemotoxylin and eosin according to the standard method using a Nikon Eclipes Ni light microscope (Japan). Antibiotic-associated liver injury occurs of the cholestatic type and is characterized by an increase in ALP, TB and the ALT/ALP ratio by two times, decomposition of the hepatic beams, moderate necrosis, fatty degeneration of hepatocytes by 7 days. The administration of LBK-527 and N-adenosyl-S-methionine reduced the toxic effect of tetracycline on the liver, which was manifested in a decrease in the activity of cytolytic icholestatic syndromes, preservation of the beam structure of the liver, degeneration and congestion in the hepatic veins. By day 14, in the control group of animals there was a decrease in the activity of intracellular enzymatic systems of hepatocytes, but complete restoration of the liver structure did not occur in comparison with the intact group. Compound LBK-527 by day 14 The area of the cytoplasm, nucleus and nuclear-cytoplasmic ratio approached the values of the intact group. The appearance of multinucleated hepatocytes indicated the activation of the synthetic activity of the liver and the launch of regeneration mechanisms. Thus, we can conclude that the pharmaceutical composition under study has a hepatoprotective effect.
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