CYP2E1 is known to be induced in
streptozotocin (STZ)-treated diabetic rats (STZ rats), and its induction is improved by
insulin. We have examined the age-dependent changes of
CYP2E1 in the liver microsomes of type 1 diabetic STZ rats, the effects of
VOSO4 on the contents of total P450 and
CYP2E1, and the activities of
CYP2E1 in terms of
p-nitrophenol hydroxylation. The contents of P450 and
CYP2E1 and
CYP2E1 activity were enhanced with the development of diabetes. When the
hyperglycemia of STZ rats was improved by daily
intraperitoneal injections of
VOSO4 for 10 days at the doses of 7 mg/kg
body weight for 5 days, 5 mg/kg for the following 3 days, and then 2.5 mg/kg for 2 days, the P450 and
CYP2E1 levels and
CYP2E1 activity were lowered than those in the untreated STZ rats. To understand the mechanism underlying CYP2E1-dependent hydroxylation activity, the production of
reactive oxygen species was examined in the
NADPH-liver microsomal systems by ESR spin-trapping.
Singlet oxygen (1O2) was detected in all microsomal systems, while
superoxide anion radical(*O2-) and
hydroxyl radical (*
OH) were not. On the basis of these results, we conclude that (1)
CYP2E1 level and activity are enhanced in the diabetic state, however, they are improved by
VOSO4 treatment, and (2) 1O2 is generated during CYP2E1-dependent substrate oxygenation.