Obesity-induced increase of CYP2E1 activity and its effect on disposition kinetics of chlorzoxazone in Zucker rats

Effects of obesity on liver cytochromes P450 in various animal models

“…In the liver, slightly higher mRNA expression of Cyp2e1 in HF and OB rats compared to ND rats was observed. In the fat, significantly higher mRNA expression of CYP2E1 in HF and OB rats compared to ND rats was seen 45 . An exception to rat obesity models was a study by Zhang et al where significantly decreased protein expression of CYP2E1 was observed in male Wistar rats.…”

“…Most studies of both human and animal obesity demonstrated increased activity and expression at protein and mRNA levels of the CYP2E1 enzyme. As a selective probe, chlorzoxazone is widely used to study the impact of obesity on CYP2E1 activity 10,44,45 . A study of obesity using human liver microsomal fractions prepared from diabetic and demographically matched nondiabetic donors observed enhanced CYP2E1 activity in diabetic fractions 44 .…”

Cytochrome P450 2E1: Its Clinical Aspects and a Brief Perspective on the Current Research Scenario

“…In Zucker rats fed a normal diet (ND), normal Zucker rats fed a high-fat diet (HF), and genetically obese Zucker rats fed a normal diet (OB) and administered CZX, the values of the area under the plasma concentration-time curve from 0 to in fi nity (AUC(in fi nity)) of CZX are in the order of ND > HF > OB rats (Khemawoot et al 2007a ) . The AUC (in fi nity) values of total 6-hydroxychlorzoxazone (6OHCZX-T), which is considered to be a CYP2E1 metabolic marker, are in the opposite order (Khemawoot et al 2007a ) . The values of the AUC (in fi nity) ratio (6OHCZX-T/ CZX) in ND, HF and OB rats are approximately 0.2, 0.3 and 0.4, respectively (Khemawoot et al 2007a ) .…”

“…The induction of CYP2E1 in obese Zucker rats and its effect on the disposition kinetics of chlorzoxazone (CZX) has been investigated (Khemawoot et al 2007a ) . In Zucker rats fed a normal diet (ND), normal Zucker rats fed a high-fat diet (HF), and genetically obese Zucker rats fed a normal diet (OB) and administered CZX, the values of the area under the plasma concentration-time curve from 0 to in fi nity (AUC(in fi nity)) of CZX are in the order of ND > HF > OB rats (Khemawoot et al 2007a ) .…”

“…The AUC (in fi nity) values of total 6-hydroxychlorzoxazone (6OHCZX-T), which is considered to be a CYP2E1 metabolic marker, are in the opposite order (Khemawoot et al 2007a ) . The values of the AUC (in fi nity) ratio (6OHCZX-T/ CZX) in ND, HF and OB rats are approximately 0.2, 0.3 and 0.4, respectively (Khemawoot et al 2007a ) . Induction of CYP2E1 protein is greater in both liver and fat of OB rats than in those of HF rats (Khemawoot et al 2007a ) .…”