Mechanisms of lindane-induced hepatotoxicity: alterations of respiratory activity and sinusoidal glutathione efflux in the isolated perfused rat liver.
1. Lindane (25-60 mg/kg) at 24 h after dosage induced a dose-dependent increase in oxygen consumption by perfused rat livers, an effect not observed at early times (2-6 h) after administration. About 60% of the increase in liver oxygen uptake is suppressed by the antioxidant, desferrioxamine, indicating enhanced free radical activity induced by the insecticide. 2. The hepatic content of total GSH equivalents (GSH + 2GSSG) decreased 4 h after lindane treatment (60 mg/kg), together with significant diminution in net and fractional rates of sinusoidal GSH efflux, that returned to control values 24 h after treatment. 3. These data indicate that lindane resulted in marked changes in hepatic oxidative capacity and glutathione metabolism, which condition the production of oxidative stress in the liver at different times of intoxication.
Videla
L A
LA
Departamento de Ciencias Biológicas, Facultad de Medicina, Universidad de Chile, Santiago.
Simizu
K
K
Barros
S B
SB
Junqueira
V B
VB
D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000503:physiopathology*; D003676:Deferoxamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000378:metabolism*; D001556:Hexachlorocyclohexane / Q000633:toxicity*; D066298:In Vitro Techniques; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010101:Oxygen Consumption / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains
D001556:Hexachlorocyclohexane; D005978:Glutathione; D003676:Deferoxamine