Sex-related differences in hepatic drug-oxidizing capacity of streptozotocin-induced diabetic rats.
Male and female animal models of diabetes were prepared by treating rats with streptozotocin (STZ). Trimethadione (TMO) metabolism was depressed in male but increased in female diabetic rats. The insulin treatment normalized rats of both sexes. Serum dimethadione/TMO ratios at 2 h correlated with the elevated blood glucose levels in male and female control, the STZ-induced diabetic and the insulin-treated diabetic rats. Treatment with STZ in male rats affected the metabolism of antipyrine, decreasing urinary excretion of norantipyrine (NORA) urine but increasing elimination of 4-hydroxyantipyrine (OHA). In female diabetic rats, the amounts of the three major metabolites, NORA, OHA and 3-hydroxymethyl-3-norantipyrine and the total (conjugate + free) were increased compared to the control. In the insulin-treated groups, these changes were normalized. In conclusion, our study showed that the effect of STZ-induced diabetes on drug metabolism varies with the sex and the drugs used. Insulin normalized all these diabetic changes.
D000818:Animals; D000983:Antipyrine / Q000378:metabolism / Q000493:pharmacokinetics / Q000652:urine; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000378:metabolism*; D004114:Dimethadione / Q000493:pharmacokinetics*; D005260:Female; D007328:Insulin / Q000627:therapeutic use; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D006899:Mixed Function Oxygenases / Q000378:metabolism; D010080:Oxazoles / Q000493:pharmacokinetics*; D010084:Oxidation-Reduction; D051381:Rats; D011919:Rats, Inbred Strains; D012737:Sex Factors; D014293:Trimethadione / Q000493:pharmacokinetics*
D007328:Insulin; D010080:Oxazoles; D004114:Dimethadione; D006899:Mixed Function Oxygenases; D014293:Trimethadione; D000983:Antipyrine