Evaluation of hepatotoxicity of "Gentabiferon-C" and "Propig" preparations upon repeated administration to laboratory mice (preclinical study)

Abstract

The study was aimed at investigating the possible toxicological effect of Gentabiferon-С and Propig on the liver of white mice (n=12). The substances were administered intramuscularly once a day for 14 days at dosages of 1/10 LD50 (550 mg/kg and 641 mg/kg, respectively) and 1/50 LD50 (110 mg/kg and 128 mg/kg, respectively). The control group animals received an equal volume of sterile 0,9% NaCl solution. The mouse liver served as the material for the study. It was isolated, macroscopically assessed, then weighed, the mass coefficient was determined, and the liver was histologically examined. Macroscopic examination of the liver of mice from the experimental and control groups did not reveal any pronounced general pathological or specific destructive changes. The organ mass coefficients did not statistically differ from the control values. Histological examination revealed the presence of focal changes in animals from the experimental groups. The severity of the adverse effects was directly dependent on the dose used. Leukocyte infiltrates were present, signs of hepatocyte nuclear polymorphism and focal cytoplasmic vacuolization were noted, as well as mild hydropic edema, which, taken together, is interpreted as a manifestation of mild dystrophy. Perivascular "cuffs", small foci of fibroblast proliferation, and collagen fiber deposits were observed, indicating the onset of fibrosis. After the recovery period (10 days), positive dynamics in the restoration of liver parenchymal tissue were observed, confirmed by the results of morphometric analysis. In the group with the most severe pathology ("Gentabiferon-С", 1/10 LD₅₀), the number of inflammatory foci decreased by 81,0%, and fibrotic foci by 73,0% (p<0,05), indicating potential reversibility of the changes. Thus, the data obtained clearly demonstrate that the hepatotoxic effect is dose-dependent, is most pronounced with high doses of "Gentabiferon-С", and is largely reversible after discontinuation of the drug.