Effect of endrin and endrin derivatives on hepatobiliary function and carbon tetrachloride-induced hepatotoxicity in male and female rats

Abstract

The effects of the cyclodiene pesticide, endrin, and its aldehyde and ketone metabolites on hepatobiliary function and CCl4-induced hepatotoxicity were investigated in Sprague-Dawley rats. The rats were given control diet or diets containing 5 or 10 ppm endrin, 10 ppm endrin aldehyde or 5 ppm endrin ketone for 15 days. Three to six rats from each treatment group were given a single ip dose (100 microliter/kg body weight) of CCl4 in corn oil (1 ml/kg) on day 15. Levels of serum glutamic-oxalacetic transaminase (SGOT), glutamic-pyruvic transaminase (SGPT), isocitrate dehydrogenase and ornithine-carbamyl transferase, bile flow and biliary excretion of an anionic model compound, phenolphthalein glucuronide (PG), were measured on day 16. Dietary treatment with endrin at either dose level did not significantly elevate serum enzyme levels, while endrin aldehyde produced a slight increase in SGOT and SGPT and endrin ketone produced a small elevation in SGPT levels. Treatment with endrin aldehyde or endrin ketone did not result in significant alterations of bile flow or biliary PG excretion. Treatment with 5 ppm endrin produced a significant reduction in bile flow and a corresponding reduction in PG excretion by male rats, whereas treatment with 10 ppm endrin reduced only the PG excretion by male rats. Female rats treated with 5 or 10 ppm endrin showed a dose-dependent choleretic effect with a commensurate increase in PG excretion. With the exception of a further slight reduction in PG excretion by male rats, treatment with the endrin or endrin derivative did not potentiate CCl4-induced alterations in hepatobiliary functions. Although the levels of some serum enzymes of rats given endrin or endrin derivatives plus CCl4 were elevated over those of rats given CCl4 alone, the increases were not of the magnitude of those that have been reported previously for chlordecone. Generally, female rats challenged with CCl4 or endrin/CCl4 exhibited greater increases in serum enzyme levels than did male rats given corresponding treatments.