Strain- and sex-related differences of carbonyl reductase activities in kidney microsomes and cytosol of rats

Abstract

This study was designed to elucidate strain- and sex-related differences of carbonyl reductase activity in rat kidney by using the oral antidiabetic drug acetohexamide as substrate. The frequency distribution of carbonyl reductase activities in kidney microsomes of male Fischer 344 (Fischer), Sprague-Dawley, Wistar and Wistar-Imamichi (Wistar-IM) rats exhibited a marked strain-related difference. Furthermore, the enzyme activities in kidney microsomes of Fischer, Sprague-Dawley and Wistar rats were male-specific, resulting insignificant sex-related differences in these strains. There was no sex-related difference of carbonyl reductase activity in kidney microsomes of the Wistar-IM strain, which lacked its activity in both sexes. On the other hand, although carbonyl reductase activities were fully detectable in kidney cytosols from all the strains of male and female rats, no strain- or sex-related difference was observed among the cytosolic enzyme activities. These results provide new information for understanding the influence of internal factors on the renal metabolism of ketone-containing xenobiotics.