The effects of
glucose on
CYP2E1 expression in rats with
acute renal failure induced by
uranyl nitrate (U-ARF) have been reported.
CYP2E1 was significantly induced (2.3-fold) in rats with U-ARF compared with that in control rats. In contrast,
CYP2E1 expression was significantly decreased in rats with U-ARF supplied with
glucose (dissolved in tap water to make 10%, w/v) in their
drinking water for 5 days (U-ARFG) compared with that in rats with U-ARF. However,
CYP2E1 in rats with U-ARFG was significantly greater than that in control rats.
Chlorzoxazone (CZX) primarily undergoes hydroxylation, catalyzed mainly by
CYP2E1, to form
6-hydroxychlorzoxazone (
OH-CZX) rats. Hence, it could be expected that in rats with U-ARFG, formation of
OH-CZX could significantly decrease and increase compared with those in rats with U-ARF and control rats, respectively. This expectation is proven by the following results of a study of
intravenous administration of CZX at a dose 20 mg/kg to control rats and rats with U-ARF and U-ARFG. First, the total area under the plasma concentration-time curve from time zero to 8 h (AUC(0-8 h)) of
OH-CZX in rats with U-ARFG (8730 microg x min/mL) was significantly greater than that in control rats (414 microg x min/mL) and significantly smaller than that in rats with U-ARF (11500 microg x min/mL). Second, the AUC(0-8 h,
OH-CZX)/AUC(CZX) ratio in rats with U-ARFG (10.0) was significantly greater than that in control rats (0.252) and significantly smaller than that in rats with U-ARF (17.5). Finally, the in vitro intrinsic
OH-CZX formation clearance (CL(int)) in rats with U-ARFG (27.9 mL/min/mg
protein) was significantly slower than that in rats with U-ARF (36.7 mL/min/mg
protein) and significantly faster than that in control rats (17.7 mL/min/mg
protein).