Affiliation:
1. Pacific State Medical University, 690002, Vladivostok, Russia
Abstract
The article presents data on the study on laboratory animals of the parameters acute and chronic toxicity a drug for pharmacocorrection of liver fibrosis - collagenase from crab hepatopancreas (collagenase CH). In a comparative study, the activity of collagenase CH significantly exceeded that of proteinases isolated from St. lavendulae and the indicators were 4.02±0.02 U/mg and 3.6±0.03 U/mg (p<0.01), respectively. A single intraperitoneal injection of the drug at a dose of 5000 mg/kg into non-linear mice caused their death within 1 day as a type of drug-induced anaphylactic shock. In the liver, circulatory hypoxia developed, up to necrosis, a sharp congestion of large vessels, plasma impregnation of their walls, aggregation and stasis in the vessels of the microvasculature, up to fibrinoid necrosis. Injection of collagenase CH in doses from 4000 mg/kg to 100 mg/kg body weight was tolerated without visible consequences throughout the entire observed period (30 days). Taking into account such data, this drug is classified as low-toxic and, according to GOST 12.1.007-76 “Harmful substances”, belongs to hazard class 4 (low-hazard substances). It has been established that collagenase CH in doses close to therapeutic (400, 200, 100 μg/kg) does not cause pronounced disturbances in liver architecture, manifested by the development of necrotic and dystrophic changes in the parenchyma. When studying chronic toxicity, the drug at the indicated concentrations does not have a toxic effect on the liver, which suggests its use for the development of new complex drugs for the treatment of fibrosis and other pathologies associated with connective tissue.