Effect of dietary lipid and dimethyl sulfoxide on lindane metabolism

Abstract

Previous investigations have suggested that there is a requirement of dietary polyunsaturated fatty acids for full expression of microsomal enzyme induction. The conclusions in these studies were primarily based on in vitro enzyme activity, sleeping time recovery, or hepatic cytochrome P-450 content, measured 24 hr after treatment with an inducing agent. This study set out to examine the influence of dietary lipids, containing different fatty acid compositions, on the storage and self-induction of lindane metabolism. The alteration in metabolism was followed on a daily basis throughout the treatment period. Twenty-four female weanling rats were fed fat-free diets either unsupplemented or supplemented with 7% hydrogenated coconut oil, 7% peanut oil, or 5% menhaden oil plus 2% linseed oil for 12 days prior to treatment with lindane. All rats then received a daily po dose of 2.5 mg of lindane in dimethyl sulfoxide (DMSO) for 7 days. On Day 8, all rats were treated with 2.5 mg of lindane (containing 1.93 μCi of [ 14C]lindane and they were sacrificed 24 hr later. Tissue samples were analyzed for radioactivity. Liver samples were assayed for microsomal phospholipid, protein, and cytochrome P-450 plus the enzymatic dehydrogenation of lindane. In addition, the fatty acid content of microsomal phosphatidylcholine (PC) and phosphatidylethanolamine (PE) was determined. Depressed food consumption and growth rate, an impaired metabolite excretion pattern, low specific microsomal phospholipid content, and a decreased microsomal PC PE ratio containing a reduced proportion of polyunsaturated fatty acids suggested that a toxic lindane-DMSO-dietary lipid interaction had occurred.