[Changes of CYP2E1 activity in diabetic rat model].
Diabetic rat model was induced by alloxan. To evaluate CYP2E1 activity indirectly, the activities of aniline dehydroxylase and other drug metabolic enzymes were measured. The pharmacokinetic profile of chlorzoxazone(CZX), a drug probe for CYP2E1, was obtained after a single oral dose of 50 mg.kg-1. The results indicated that diabetes increased aniline dehydroxylase activity by 53%. The Cmax and AUC of chlorzoxazone in diabetic rats were reduced 37% and 34%, respectively. The Tpeak of 6-hydroxychlorzoxazone in diabetic rats was shortened apparently. The hydroxylation index described by the AUC ratio of 6-hydroxychlorzoxazone to chlorzoxazone or the ratio of concentration of 6-hydroxychlorzoxazone to chlorzoxazone, which indicated the ability of hydroxylation, was increased in diabetes. In conclusion, diabetes can induce CYP2E1 activity, suggesting that diabetic patients should be cautious when taking some therapeutic drugs which metabolized by CYP2E1.
Li
L
L
Department of Pharmacology, Beijing Medical University, Beijing 100083.
Zhang
Y
Y
D000815:Aniline Hydroxylase / Q000378:metabolism; D000818:Animals; D002753:Chlorzoxazone / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics; D019392:Cytochrome P-450 CYP2E1 / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology*; D008297:Male; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley
C039289:6-hydroxychlorzoxazone; D019392:Cytochrome P-450 CYP2E1; D000815:Aniline Hydroxylase; D002753:Chlorzoxazone