Endrin-induced increases in hepatic lipid peroxidation, membrane microviscosity, and DNA damage in rats.
Endrin is a polyhalogenated cyclic hydrocarbon pesticide which produces hepatic and neurologic toxicity. Previous studies have indicated that endrin induces hepatic lipid peroxidation. In order to further assess the possible role of lipid peroxidation in the toxicity of endrin, the dose- and time-dependent effects of endrin on hepatic lipid peroxidation, membrane microviscosity and DNA damage in rats were examined. Rats were treated with 0, 3.0, 4.5, or 6.0 mg endrin/kg as a single oral dose in corn oil, and the animals were killed 0, 12, 24, 48, or 72 h post-treatment. Dose-dependent increases in hepatic mitochondrial and microsomal lipid peroxidation and microviscosity as well as nuclear DNA single strand breaks were observed as early as 12 h post-treatment. Maximum increases in these three parameters occurred 24 h after endrin administration at all three doses. While the incidence in DNA damage decreased with time after 24 h, the incidence of lipid peroxidation and microviscosity of microsomal and mitochondrial membranes remained relatively constant. Dose- and time-dependent increases in liver and spleen weight/body weight ratios with decreases in thymus weight/body weight ratios were observed. The data indicate that endrin administration induces hepatic lipid peroxidation which may be responsible for the increased membrane microviscosity as a result of membrane damage as well as enhanced DNA damage.
Bagchi
M
M
Department of Pharmaceutical Sciences, Creighton University Health Sciences Center, Omaha, Nebraska 68178.
Hassoun
E A
EA
Bagchi
D
D
Stohs
S J
SJ
D000704:Analysis of Variance; D000818:Animals; D004249:DNA Damage / Q000502:physiology*; D004732:Endrin / Q000633:toxicity*; D005260:Female; D007425:Intracellular Membranes / Q000187:drug effects*; D015227:Lipid Peroxidation / Q000187:drug effects*; D008099:Liver / Q000187:drug effects*; D008560:Membrane Fluidity / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains
D004732:Endrin