A higher incidence of convulsions and loss of the righting reflex, and decreased rates of survival, as well as elevated CYP2E1 activity, were observed in diabetic rats treated with AN when compared to those in non-diabetic rats, suggesting that diabetes confers susceptibility to the acute toxicity of AN.
The present work firstly reported that Hon treatment ameliorated the abnormal change of hepatic CYP activity (including CYP2E1, CYP4A and CYP1A2) and the transporter mRNA expression (including hepatic Oat2 and Oatp2b1, renal Bcrp and Mrp4) in type 2 diabetic rats induced by high-fat diet and strepotozotocin, which are associated with the occurrence and development of diabetes.
Interestingly, CYP2E1 isoforms expressed in both endoplasmic reticulum (ER) and mitochondria, likely lead to the deleterious consequences in response to alcohol or in conditions of NAFLD after exposure to high fat diet (HFD) and in obesity and diabetes.
CYP2E1 can play a crucial role in stress-induced pathological processes in the liver in diabetes, and the inhibition of the enzyme by quercetin during the development of diabetes mainly prevents the oxidative damage in liver.
CYP2E1 protein was significantly increased (16-fold) by diabetes, leading to a reduction in levels of the potent vasoconstrictor 20-hydroxy-eicosatetraenoic acid (20-HETE).
Part of the reason for conflicting evidence regarding genotype effect on phenotype may be due to the wide variety of exposures such as ethanol or dietary factors and physiological factors including body weight or diabetes that modulate CYP2E1 expression.