title: Liver microsomal parameters related to oxidative stress and antioxidant systems in hyperthyroid rats subjected to acute lindane treatment.
abstract: Liver microsomal functions related to xenobiotic biotransformation and free radical production were studied in control rats and in animals subjected to L-3,3',5-triiodothyronine (T3) and/or lindane administration as possible mechanisms contributing to oxidative stress, in relation to the activity of enzymes (superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), and glucose-6-phosphate dehydrogenase (G-6PDH)) and content of lipid-soluble vitamins (alpha-tocopherol, beta-carotene, and lycopene) affording antioxidant protection. Lindane treatment in euthyroid rats at a dosage of 20mg/kg did not modify the content of liver microsomal cytochromes P450 and b5, the activity of NADPH-cytochrome P450 reductase and NADH-cytochrome b5 reductase, and the production of superoxide radical (O2.-), as well as antioxidant systems, except for the reduction in lycopene levels. Hyperthyroidism elicited a calorigenic response and increased specific and molecular activities of NADPH-cytochrome P450 reductase, O2.- generation, and G-6PDH activity, concomitantly with diminution in liver SOD and catalase activities and in alpha-tocopherol, beta-carotene, and lycopene levels. The administration of lindane to hyperthyroid animals led to a further increase in the molecular activity of NADPH-cytochrome P450 reductase and in the O2.- production/SOD activity ratio, and decrease of hepatic alpha-tocopherol content, in a magnitude exceeding the sum of effects elicited by the separate treatments, as previously reported for reduced glutathione depletion. Collectively, these data support the contention that the increased susceptibility of the liver to the toxic effects of acute lindane treatment in hyperthyroid state is conditioned by potentiation of the hepatic oxidative stress status.
authors.affiliation: Departamento de Bioquímica, Instituto de Química, Universidade de Sâo Paulo, Brasil.
authors.forename: K A
authors.initials: KA
authors.lastname: Simon Giavarotti
authors.forename: L
authors.initials: L
authors.lastname: Rodrigues
authors.forename: T
authors.initials: T
authors.lastname: Rodrigues
authors.forename: V B
authors.initials: VB
authors.lastname: Junqueira
authors.forename: L A
authors.initials: LA
authors.lastname: Videla
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D001711:Biotransformation; D002338:Carotenoids / Q000378:metabolism; D002374:Catalase / Q000187:drug effects / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects / Q000378:metabolism; D005954:Glucosephosphate Dehydrogenase / Q000187:drug effects / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000187:drug effects / Q000378:metabolism; D001556:Hexachlorocyclohexane / Q000494:pharmacology*; D006980:Hyperthyroidism / Q000188:drug therapy / Q000378:metabolism*; D000077276:Lycopene; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism*; D009247:NADH, NADPH Oxidoreductases / Q000187:drug effects / Q000378:metabolism; D009251:NADPH-Ferrihemoprotein Reductase; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000187:drug effects / Q000378:metabolism; D014284:Triiodothyronine / Q000494:pharmacology; D014810:Vitamin E / Q000378:metabolism; D019207:beta Carotene / Q000378:metabolism
chemical_list: D000975:Antioxidants; D017382:Reactive Oxygen Species; D019207:beta Carotene; D014284:Triiodothyronine; D014810:Vitamin E; D002338:Carotenoids; D001556:Hexachlorocyclohexane; D003577:Cytochrome P-450 Enzyme System; D005954:Glucosephosphate Dehydrogenase; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D009247:NADH, NADPH Oxidoreductases; D009251:NADPH-Ferrihemoprotein Reductase; D000077276:Lycopene