Differences in hepatic drug metabolizing enzymes and their response to lindane in rat, rabbit and monkey.
Untreated rabbit liver microsomes demonstrated the highest content of cytochrome P450 and activity of NADPH cytochrome c reductase compared to rat and monkey. The sodium dodecyl sulfate polyacrylamide gel electrophoresis of microsomes from untreated rabbit demonstrated a greater quantity of 50 KDa polypeptide than in rat and monkey. The activity of glutathione-S-transferase towards 1-chloro-2,4-dinitrobenzene and the band intensity of 26 KDa polypeptide was found to be at maximum in untreated rabbits, while rat liver demonstrated the highest activity of glutathione-S-transferase towards ethacrynic acid. The extent of hepatic microsomal lipid peroxidation was at maximum in untreated rats. The activity of catalase was higher in untreated monkeys compared to untreated rats and rabbits. Lindane at a dose of 10 mg kg-1 body weight for a period of six days increased the hepatic content of cytochrome P450 and the activities of NADPH cytochrome c reductase, aminopyrine N-demethylase, glutathione-S-transferases, haem oxygenase and lipid peroxidation, decreased non-protein thiols and concomitantly intensified the 50 and 26 KDa polypeptides in the microsomes and 100,000 x g supernatants respectively, in the rat but not in the rabbit or monkey. The results demonstrate that lindane is a bifunctional inducer in the rat and non-functional in rabbit and monkey. It also increased the activities of hepatic drug metabolizing enzymes with concomitant production of oxidative stress in the rat, whereas in rabbit and monkey it did not alter the drug metabolizing enzymes nor produced any oxidative stress.
Puri
S
S
Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Kohli
K K
KK
D000633:Aminopyrine N-Demethylase / Q000378:metabolism; D000818:Animals; D002374:Catalase / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects / Q000378:metabolism; D004137:Dinitrochlorobenzene / Q000633:toxicity; D004591:Electrophoresis, Polyacrylamide Gel; D004976:Ethacrynic Acid / Q000633:toxicity; D005982:Glutathione Transferase / Q000187:drug effects / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D001556:Hexachlorocyclohexane / Q000633:toxicity*; D007306:Insecticides / Q000633:toxicity*; D007509:Irritants / Q000633:toxicity; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008253:Macaca mulatta; D008970:Molecular Weight; D009251:NADPH-Ferrihemoprotein Reductase / Q000187:drug effects / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D013045:Species Specificity
D004137:Dinitrochlorobenzene; D007306:Insecticides; D007509:Irritants; D001556:Hexachlorocyclohexane; D003577:Cytochrome P-450 Enzyme System; D002374:Catalase; D006419:Heme Oxygenase (Decyclizing); D000633:Aminopyrine N-Demethylase; D009251:NADPH-Ferrihemoprotein Reductase; D005982:Glutathione Transferase; D004976:Ethacrynic Acid