The responses of hepatic monooxygenases of guinea pig to cadmium and nickel.
When Cd (3.58 mg CdCl2.H2O/kg, ip) was administered to male guinea pigs 72 h prior to sacrifice, the metal significantly inhibited the aniline 4-hydroxylase (AH) (16%), ethylmorphone N-demethylase (EMND) (26%), and aminopyrine N-demethylase (AMND) (18%) activities and cytochrome P-450 (12%) and cytochrome b5 (10%) levels. Cd did not alter the hepatic microsomal heme level. Cd, however, significantly increased the hepatic microsomal p-nitroanisole O-demethylase (p-NAOD) (53%) activity. When Ni (59.5 mg NiCl2 x 6H2O/kg, sc) was administered to the guinea pigs 16 h prior to sacrifice, the metal significantly depressed AH (49%), p-NAOD (66%), EMND (47%), and AMND (37%) activities, and cytochrome P-450 (15%), cytochrome b5 (24%), and microsomal heme (28%) levels. For the combined treatment, animals received the single dose of Ni 56 h after the single dose of Cd and then were killed 16 h later. In these animals, significant inhibitions were noted in AH (51%), EMND (47%), and AMND (30%) activities, and cytochrome P-450 (15%), cytochrome b5 (26%), and microsomal heme (30%) compared to those of controls. In the case of p-NAOD activity, the influence was in favor of Ni, i.e., the inhibition was about 61% by the combined treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
Işcan
M
M
Department of Toxicology, Faculty of Pharmacy, Ankara University, Tandogan, Turkey.
Coban
T
T
Eke
B C
BC
Işcan
M
M
D000633:Aminopyrine N-Demethylase / Q000037:antagonists & inhibitors; D000815:Aniline Hydroxylase / Q000037:antagonists & inhibitors; D000818:Animals; D002104:Cadmium / Q000633:toxicity*; D065607:Cytochrome P-450 Enzyme Inhibitors; D006168:Guinea Pigs; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D009532:Nickel / Q000633:toxicity*; D009575:Nitroanisole O-Demethylase / Q000037:antagonists & inhibitors; D010088:Oxidoreductases / Q000037:antagonists & inhibitors*
D065607:Cytochrome P-450 Enzyme Inhibitors; D002104:Cadmium; D009532:Nickel; D009575:Nitroanisole O-Demethylase; D010088:Oxidoreductases; D000815:Aniline Hydroxylase; D000633:Aminopyrine N-Demethylase