Sex differences in stereospecificity of oracin reductases in rat in vitro and in vivo

In vitro and in vivo experiments to investigate possible stereospecific asp ects of oracin reduction in relation to rat gender have been conducted. Inc ubation of oracin with rat microsomes, cytosol, and hepatocytes in the pres ence of various coenzymes and under aerobic or anaerobic conditions provide d evidence for sex differences in the formation of 11-dihydrooracin (DHO) e nantiomers. The greatest sex differences were seen in hepatocytes where fem ales showed higher stereospecificity of the reductases than males. While fe male biotransformation enzymes preferentially generated approximately 82% o f (+)-DHO, male enzymes gave only rise to 63% of (+)-DHO. Males displayed h igher stereospecificity than females in the microsomal fraction. However, i n the cytosolic fraction females exhibited higher stereospecificity than ma les. Similarly, in in vivo studies, the ratio of (+)- and (-)-DHO in faeces and urine gave no indication of the significant differences between the ma le and female rat. Enzyme stereospecificity has been defined as preferentia l formation of the (+)- or (-)-stereoisomer of 11-DHO by the respective enz yme. HPLC quantitative determinations of both enantiomers were performed us ing a Chiralcel OD-R column as the chiral stationary phase with excellent r esolution and stability. Chirality 11:505-509, 1999. (C) 1999 Wiley-Liss, I nc.