A comparison of some effects of dimethyl sulphoxide and dimethyl sulphone on rat liver microsomal enzymes

Abstract

Dimethyl sulphone, while inactive as a hepatic microsomal enzyme stimulator when injected into rats, caused a significant increase in the enzymic formation of paraaminophenol when added in vitro to incubation systems containing microsomes plus cofactors plus aniline. This response, which was associated with changes in K m and V max for aniline metabolism in vitro, was similar to that obtained after treating rats with dimethyl sulphoxide (DMSO). However at least 10 6 times as much dimethyl sulphone had to be added in vitro to give a comparable response to that found after injection of effective doses of 14C labeled DMSO. The DMSO treatment of rats was found to change the pH optimum of hepatic microsomal aniline hydroxylase from 7.1 to 6.7, and to increase the microsomal NADPH-cytochrome P-450 reductase activity. Neither of these results were found after in vitro addition of dimethyl sulphone to hepatic microsomes. The apparent additive effect on microsomal aniline para-hydroxylase of DMSO pretreatment of rats and dimethyl sulphone addition in vitro to microsomes also suggests that these two chemicals stimulate this enzyme by different mechanisms.