Regression of morphological alterations and oxidative stress-related parameters after acute lindane-induced hepatotoxicity in rats.
Changes in rat liver oxidative stress-related parameters, morphological alterations, as well as circulating and tissue levels of lindane were studied 1-7 days after the administration of a single dose of 60 mg of lindane/kg. One day after lindane treatment, a significant enhancement in the oxidative stress status of the liver was observed, characterized by an increase in thiobarbituric acid reactants production and in the microsomal generation of superoxide radical (O.-2) coupled to cytochrome P450 induction, and a decrement in the activity of superoxide dismutase (SOD) and catalase. Consequently, the O.-2 production/SOD activity ratio was enhanced two-fold. In this condition, light microscopy studies revealed the incidence of liver lesions in periportal areas, together with significant changes at the mitochondrial level observed by electron microscopy, which coincide with the maximal levels of lindane in the liver, adipose tissue, plasma and whole blood. Changes in oxidative stress-related parameters observed after 1 day of lindane treatment regressed to normal from the third day and thereafter, together with the decrement in circulating and tissue levels of the insecticide. It is concluded that morphological and oxidative stress-related changes induced in the liver by acute lindane intoxication are readily reversible, depend on the hepatic content of the insecticide, and seem to be conditioned by the changes in O.-2 generation.
Junqueira
V B
VB
Departmento de Bioquímica, Universidade de Säo Paulo, Brasil. vbcjunqu@quim.iq.usp.br
Koch
O R
OR
Arisi
A C
AC
Fuzaro
A P
AP
Azzalis
L A
LA
Barros
S B
SB
Cravero
A
A
Farré
S
S
Videla
L A
LA
D000273:Adipose Tissue / Q000737:chemistry; D000818:Animals; D002374:Catalase / Q000187:drug effects / Q000378:metabolism; D001556:Hexachlorocyclohexane / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity*; D066298:In Vitro Techniques; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008854:Microscopy, Electron; D008928:Mitochondria / Q000648:ultrastructure; D015388:Organelles / Q000648:ultrastructure; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000187:drug effects / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014018:Tissue Distribution
D017392:Thiobarbituric Acid Reactive Substances; D001556:Hexachlorocyclohexane; D002374:Catalase; D013482:Superoxide Dismutase