EFFECT OF LINDANE ON INTESTINAL NITROREDUCTASE, AZOREDUCTASE, BETA-GLUCURONIDASE, DECHLORINASE, AND DEHYDROCHLORINASE ACTIVITY

It has been reported that pretreatment of rats with the organochlorine insecticide γ-hexachlorocyclohexane (lindane) significantly increases nitroreductase activity as well as the biotransformation of parathion to aminoparathion in the intestinal tract of rats. Such an interaction could affect the metabolism, toxicity, and risk assessment of many environmental nitro compounds that become toxic, mutagenic, or carcinogenic upon reduction of their nitro groups. This study was conducted to determine: (i) the effect of lindane on the activity of five microbial enzymes in the intestinal tract; (ii) possible regional differences in the effect of lindane; (iii) whether the enzymes selected for study were exclusively of microbial origin; and (iv) how lindane produced the effect. Weanling male and female Fischer 344 rats received daily po injections of 20 mg/kg lindane in peanut oil for 2 or 5 weeks while controls received the vehicle. After 4 weeks, half the remaining treated animals were transferred to isolation cubicles and received antibiotics in addition to their regular treatment. At autopsy, the small intestine and cecum were aseptically excised, homogenized, and incubated with a dimethyl sulfoxide mixture of p,p′-DDT, 3,4-dichloronitrobenzene, p-nitrophenyl β-d-glucuronide, and methyl orange. After 2 weeks, lindane produced significantly higher β-glucuronidase activity in the small intestine and significantly greater dechlorinase and azoreductase activity in the cecum. After 5 weeks, lindane significantly increased nitroreductase and azoreductase activity in the small intestine. Coadministration of antibiotics with lindane markedly reduced the microbial flora in both the small intestine and cecum. However, whereas enzyme activity in the cecum of the treated rats was decimated, enzyme activity in the small intestine of these animals was reduced to a level not significantly below that of the controls. Thus, while increased enzyme activity in the small intestine of the lindane-treated rats appears to be of microbial origin, substantial amounts of mucosal enzyme may also be present in this region. © 1990.