A comparative study of the effects of cadmium and nickel on liver microsomal drug metabolizing enzymes of guinea-pig in vitro

1. 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 NiCl₂.2. 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.3. When the liver 10,000 g supematants 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.4. 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.