EXPRESSION OF GAMMA-GLUTAMYLTRANSFERASE IN RAT HEPATOCYTES EXPOSED TO GENERIC CARBENDAZIM ON THE MODEL OF «NDEA- HEPATECTOMY»

Lisovska V. S.

CLINICAL AND EXPERIMENTAL MEDICINE

Scentific article

Carbendazim classified (1986 y) as C-group carcinogen (possible human carcinogen) by experts from the United States Environmental Protection Agency (EPA). This conclusion is based on the results of chronic actions of the original drug, which were conducted in the 70’s and 80’s. According to them, mice of CD-1 and Swiss lines showed an increase trend in the hepatocellular carcinoma and increase trend in the combined hepatocellular tumor (adenomas and/or carcinoma). Possible mechanisms of action, which lead to the induction of liver tumors by the action of carbendazim, are debatable. Hepatocarcinogenicity of carbodazim in a chronic experiment without the first evidence of genotoxic composition, namely, the absence of data on the induction of aneuploidy in the target organ, suggests the promoter properties of the substance. Objective: identification of carbendazime promoter properties in rat hepatocytes initiated of N-Nitrosodiethylamine by the level expression of gamma-glutamyltransferase. The object and methods of research. A generic Chinese made 98% carbendazim was used in the study. It was conducted on the model «NDEA-hepatectomy» in the mid-term experiment (Ito N, et al., 1992). A total of 50 male rats Wistar 200-250 g weight were used, there were 5 groups: 1 – negative control (vehicle); 2 – positive control (phenobarbital at a dose of 37.5 mg/kg); groups 3, 4 and 5 – carbendazim at doses of 25, 75 and 300 mg/ kg. Carbendazim was administered to animals for 8 weeks orally by gavage. General condition and body weight of animals were estimated. After euthanasia and necropsy, a histochemical analysis (azo coupling method) was conducted by GGT activity in liver tissue – the number and area of GGT positive foci were determined. Results. The study did not reveal the toxic effect of carbendazim on the rat organisms – condition of the animals, body weight and macroscopy of the internal organs and tissues of the experimental animals were similar to the negative control. According to morphometric parameters of GGT positive foci at a dose of 25 mg/kg, the effect appeared to be not reliable. At a dose of 75 mg/kg, increasing of foci number and a tendency to increasing their area were revealed, which indicates on the pre-neoplastic hepatocytes proliferation. At a dose of 300 mg/kg a statistical increasing indices compared with the negative control was not established. Conclusions 1. The number and area of GGT positive foci in the liver of animals did not increase at minimal and maximal doses (25 and 300 mg/kg), at the mid dose (75 mg/kg) the number of foci increased.2. Characteristic of carbendazime promoter action is absence of dose-effect relation which may indicate a «paradoxical» nature of effect. 3. Carbendazim demonstrates low promoter effect on hepatocarcinogenesis.

Carbendazim, hepatocarcinogenesis, «NDEA-hepatectomy», pre-neoplastic changes, gammaglutamyltransferase, liver, rats.

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«Bulletin of problems biology and medicine» Issue 4 Part 2 (154), 2019 year, 130-135 pages, index UDK 591.133.2:616.36-006:615.9:632.95

10.29254/2077-4214-2019-4-2-154-130-135