A comparative study of the effects of cadmium and nickel on liver microsomal drug metabolizing enzymes of guinea-pig in vitro.
In vitro addition of cadmium chloride (CdCl2) or nickel chloride (NiCl2) to an incubation mixture produced a concentration-dependent inhibition of liver microsomal aniline 4-hydroxylase activity of male guinea-pig. The inhibitory effect of CdCl2 on the enzyme activity was stronger than that of NiCl2. While CdCl2 also caused a concentration-dependent inhibition of liver microsomal ethylmorphine N-demethylase activity, NiCl2 increased the enzyme activity between the concentrations 10(-5) and 10(-3) M and caused a rather abrupt decline at higher concentrations. When the liver 10,000 g supernatants were preincubated in the presence of metals, metal-induced inhibitions increased as the time of preincubation progressed and attained their maximal rates at about 5 and 15 min for microsomal aniline 4-hydroxylase and ethylmorphine N-demethylase activities, respectively. However, no change was noted by NiCl2 on liver microsomal ethylmorphine N-demethylase activity as the time of preincubation progressed. After preincubations, the concentration-dependent inhibitions produced by metals on liver microsomal drug metabolizing enzyme activities were found to be stronger and in favour of CdCl2.
D000815:Aniline Hydroxylase / Q000378:metabolism; D000818:Animals; D001711:Biotransformation; D002104:Cadmium / Q000494:pharmacology*; D005037:Ethylmorphine-N-Demethylase / Q000378:metabolism; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D009532:Nickel / Q000494:pharmacology*; D013997:Time Factors
D002104:Cadmium; D009532:Nickel; D006899:Mixed Function Oxygenases; D000815:Aniline Hydroxylase; D005037:Ethylmorphine-N-Demethylase