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.

Oxidative Stress and Antioxidant Status in Hypo- and Hyperthyroidism

“…The organism can defend itself against the effects of oxidative stress by increasing SOD activity as a protection mechanism, but we observed a decreased SOD activity in our study. The observed diminution of SOD activity in rats, following L-thyroxine treatment can be correlated with the observations of [184]. However, our results are not in good agreement with the findings of [141] and [185], who noticed that hyperthyroidism induced in rats by T3 caused an elevation of SOD activity in liver.…”

Thyroid hormone-induced oxidative stress

“…These changes related to oxidative stress were dose [145] and time [143] dependent, and coincided with the onset and progression of morphological lesions [143]. Studies concerning the effects of thyroid hormone on lindane hepatotoxicity showed that combined lindane-T 3 administration increased ROS production [145,146], and GSH [146] and a-tocopherol [147] depletion to an extent that exceeded the sum of the effects elicited by the separate treatments, concomitantly with extensive liver necrosis. In the whole, these data support the view that the increased liver susceptibility to lindane intoxication in hyperthyroidism depends on potentiation of tissue oxidative stress.…”

Effects of Triiodothyronine-induced Hyperthyroidism on Lipid Peroxidation, Erythrocyte Resistance and Iron-binding and Iron-oxidizing Antioxidant Properties of Plasma in the Rabbit

“…Printed in the Netherlands peroxide levels (Ferna¨ndez et al, 1985;Asayama et al, 1987). More recent studies have indicated that hyperthyroidism induced by administration of triiodothyronine (T 3 ) a¡ects tissue oxidative stress parameters and alters various cellular defence mechanisms in the liver (Troncoso et al, 1997;Huh et al, 1998;Simon-Giavarotti et al, 1998;Tapia et al, 1999;Venditti et al, 1999), heart (Venditti et al, 1997;LopezTorres et al, 2000) and some skeletal muscles (Venditti et al, 1997) of the rat.…”