Enhancement of lindane-induced liver oxidative stress and hepatotoxicity by thyroid hormone is reduced by gadolinium chloride.
The role of Kupffer cells in the hepatocellular injury and oxidative stress induced by lindane (20 mg/kg; 24h) in hyperthyroid rats (daily doses of 0.1 mg L-3,3',5-triiodothyronine (T3)/kg for three consecutive days) was assessed by the simultaneous administration of gadolinium chloride (GdCl3; 2 doses of 10mg/kg on alternate days). Hyperthyroid animals treated with lindane exhibit enhanced liver microsomal superoxide radical (O2.-) production and NADPH cytochrome c reductase activity, with lower levels of cytochrome P450, superoxide dismutase (SOD) and catalase activity, and glutathione (GSH) content over control values. These changes are paralleled by a substantial increase in the lipid peroxidation potential of the liver and in the O2.- generation/ SOD activity ratio, thus evidencing a higher oxidative stress status that correlates with the development of liver injury characterized by neutrophil infiltration and necrosis. Kupffer cell inactivation by GdCl3 suppresses liver injury in lindane/T3-treated rats with normalization of altered oxidative stress-related parameters, excepting the reduction in the content of GSH and in catalase activity. It is concluded that lindane hepatotoxicity in hyperthyroid state, that comprises an enhancement in the oxidative stress status of the liver, is largely dependent on Kupffer cell function, which may involve generation of mediators leading to pro-oxidant and inflammatory processes.
Simon-Giavarotti
Karin A
KA
Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo, Brasil. karsimon@bol.com.br
Giavarotti
Leandro
L
Gomes
Ligia F
LF
Lima
Alessandra F
AF
Veridiano
Adriano M
AM
Garcia
Eduardo A
EA
Mora
Oswaldo A
OA
Fernández
Virginia
V
Videla
Luis A
LA
Junqueira
Virginia B C
VB
D000818:Animals; D002374:Catalase / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004734:Energy Metabolism; D005682:Gadolinium / Q000008:administration & dosage*; D001556:Hexachlorocyclohexane / Q000008:administration & dosage / Q000633:toxicity*; D006980:Hyperthyroidism / Q000139:chemically induced / Q000378:metabolism*; D007728:Kupffer Cells / Q000473:pathology / Q000502:physiology; D008099:Liver / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013481:Superoxides / Q000378:metabolism; D014284:Triiodothyronine
D014284:Triiodothyronine; D013481:Superoxides; D001556:Hexachlorocyclohexane; D003577:Cytochrome P-450 Enzyme System; D005682:Gadolinium; D002374:Catalase; D009251:NADPH-Ferrihemoprotein Reductase; C038958:gadolinium chloride