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.