Differential responses of hepatic monooxygenases and glutathione S-transferases of mice to a combination of cadmium and nickel.
The acute combined effects of cadmium (Cd) and nickel (Ni) on hepatic monooxygenase activities (ethylmorphine N-demethylase, EMND; aminopyrine N-demethylase, AMND; aniline 4-hydroxylase, AH), cytochrome P-450, cytochrome b5, microsomal heme and reduced glutathione (GSH) levels and glutathione S-transferase (GST) activities toward several substrates (1-chloro-2,4-dinitrobenzene, CDNB; 1,2-dichloro-4-nitrobenzene, DCNB; ethacrynic acid, EAA; 1,2-epoxy-3-(p-nitrophenoxy)-propane, ENPP) were determined and compared with those of Cd or Ni alone in mice. Male adult mice (25-30 g) were administered either a single dose of Cd (3.58 mg CdCl2.H2O/kg, i.p.) 48 hr prior to killing or a single dose of Ni (59.5 mg NiCl2.H2O/kg, s.c.) 16 hr prior to killing. For the combined treatment, the animals received the single dose of Ni 32 hr after the single dose of Cd and were then killed 16 hr later. Cd treatment alone significantly decreased EMND, AMND, and AH activities and cytochrome P-450 and heme levels as compared with controls. Cytochrome b5 level was not altered by Cd treatment. Cd also inhibited GSH level and the GST activities toward CDNB, EAA and ENPP significantly. No significant change was observed in the GST activity for DCNB by Cd. Ni treatment alone, however, decreased the monooxygenase and GST activities studied, and cytochrome P-450, cytochrome b5, heme and GSH levels significantly. Combined treatment significantly depressed the monooxygenase activities and cytochromes and heme levels. GSH level was not significantly altered.(ABSTRACT TRUNCATED AT 250 WORDS)
Iscan
M
M
Department of Toxicology, Faculty of Pharmacy, Ankara University, Turkey.
Coban
T
T
Eke
B C
BC
Iscan
M
M
D000815:Aniline Hydroxylase / Q000378:metabolism; D000818:Animals; D002104:Cadmium / Q000633:toxicity*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D015786:Cytochromes b5 / Q000378:metabolism; D004137:Dinitrochlorobenzene / Q000378:metabolism; D004357:Drug Synergism; D004852:Epoxy Compounds / Q000378:metabolism; D004976:Ethacrynic Acid / Q000378:metabolism; D005037:Ethylmorphine-N-Demethylase / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism*; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D051379:Mice; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D009532:Nickel / Q000633:toxicity*; D009578:Nitrobenzenes / Q000378:metabolism; D009596:Nitrophenols / Q000378:metabolism; D011480:Protease Inhibitors / Q000378:metabolism; D013379:Substrate Specificity
D004137:Dinitrochlorobenzene; D004852:Epoxy Compounds; D009578:Nitrobenzenes; D009596:Nitrophenols; D011480:Protease Inhibitors; D002104:Cadmium; D009532:Nickel; D015786:Cytochromes b5; D003577:Cytochrome P-450 Enzyme System; C007606:1,2-epoxy-3-(p-nitrophenoxy)propane; C028328:1,2-dichloro-4-nitrobenzene; D006899:Mixed Function Oxygenases; D000815:Aniline Hydroxylase; D005037:Ethylmorphine-N-Demethylase; D005982:Glutathione Transferase; D005978:Glutathione; D004976:Ethacrynic Acid