Lindane Administration Research Articles

In vitro benzo[ a]pyrene metabolism from lindane-treated rat liver: Effect of oral and acute administration, and comparison with phenobarbital and methylcholanthrene pretreatment

Lindane (γ-hexachlorocyclohexane) was given orally to Sprague-Dawley male rats in their basal diet, at 24, 120, and 240 ppm, for 4 weeks. Acute intoxication was obtained with ip injection, at 20 mg/kg/day for 3 consecutive days, and the inductive effect was compared to phenobarbital (ip, 80 mg/kg/day for 3 days) and methylcholanthrene (ip, 20 mg/kg/day for 3 days) pretreatment. The spectrofluorometric measurement of arylhydrocarbon hydroxylase (AHH) activity did not show any induction after lindane and phenobarbital pretreatment, while the quantitative determination of benzo[ a]pyrene (BP) metabolites by thin-layer chromatography indicated an increase of 3-hydroxy-BP (3-OH-BP). Differences in the BP/protein ratio could explain this discrepancy. Consequently, lindane appeared as a weaker inducer of AHH activity than phenobarbital. The in vitro binding of [ 14C]BP metabolites to DNA was largely enhanced by the oral administration of lindane from as low as 24 ppm in the diet and seemed dose related until 120 ppm, reaching two or three times the control value. The acute intoxication by lindane resulted in an increase in BP metabolite binding to DNA similar to that obtained with 120 ppm in the diet. From the chromatographic pattern of BP metabolites, it is concluded that lindane induced a large formation of 4,5-BP-dihydrodiol, which was related to a two-fold increase in epoxide-hydratase activity. From these results, lindane could be considered as a phenobarbital-like inducer.

The effect of lindane and phenobarbital on microsomal enzyme induction in dogs and miniature swine

The enzymic activities of 9000 g supernatant fractions obtained from the livers of normal beagle dogs and miniature swine and of dogs and swine treated with lindane and phenobarbital are presented. No significant sex differences in activities were noted in control dogs. Preparations from dogs of both sexes fed lindane at 7.5 and 15.0 mg/kg exhibited a significant loss in codeine demethylase activity while nitroreductase activity was increased twofold. Phenobarbital pretreatment of dogs and swine stimulated all microsomal systems tested. Addition of lindane to the diet of these induced dogs caused a significant and rapid decline in the values after only two feedings. Enzymes induced to a greater extent in dogs by phenobarbital were inhibited to a greater extent by lindane; i.e., as a class, demethylases were affected by both lindane and phenobarbital to a greater extent than aromatic hydroxylases. In contrast, administration of lindane to phenobarbitaltreated swine caused an actual further increase in demethylase activities. A decrease in the induced state was observed in aromatic hydroxylation, azo-reduction, and nitro-reduction reactions, although the activities of these enzymes were still higher than the values from control swine.

Effect of intratesticular injection of lindane and endrin on the testes of rats.

Little is known about the action of different insecticides on the testicular tissue of animals. The administration of lindane and endrin into the rat testis produced hypertrophic and atrophic changes in the testis and induced total arrest of spermatogenesis. Unlike cytotoxic or alkylating agents, the action of these two insecticidal compounds was non‐specific to any group of spermatogenic cells. Intertubular and intratubular regions of the testis showed degenerative changes, necrosis and cellular proliferation. The seminiferous epithelium of the tubules was completely damaged. Formation of multinucleate giant cells of the foreign body type reaction was very common following lindane treatment. The number of spermatozoa and the percentage of deformed (abnormal) spermatozoa was very low after lindane administration as compared to that of endrin.