Quercetin prevents type 1 diabetic liver damage through inhibition of CYP2E1

Background: Increased CYP2E1 protein and activity levels can be the main cause of stress-mediated liver damage in diabetes. In this work we investigated the quercetin properties to prevent diabetic oxidative liver injury through inhibition of CYP2E1. Methods: Animals were randomly divided into three groups (n = 5 for each group): non-diabetic control, STZ-diabetic rats and STZ-diabetic rats administered with quercetin (50 mg/kg bw, per day, during 30 days). Markers of oxidative stress and liver injury, hepatocyte ultrastructure and levels of CYP2E1 protein and activity were examined using biochemical, electron microscopy and molecular biological methods. Results: It was shown that symptoms of diabetes (hyperglycemia, bodyweight loss, damaged hepatocyte ultrastructure), signs of oxidative stress in liver (2-fold intensification of peroxide process and 2-fold depletion of antioxidants) and serum markers of liver damage (3.5-, 1.5- and 5-fold increase in levels of ALT, AST and GGT, respectively) were present in STZ-diabetic rats. We found 3- and 2.5-fold increase in levels of protein and activity of CYP2E1 in the liver of STZ-diabetic rats. We demonstrated that the administration of quercetin leads to significant decrease in CYP2E1 activity (5- and 2-times compared to STZ-diabetic and control group, respectively). That was accompanied by normalization of pro-oxidant-antioxidant balance, improving the ultrastructure of hepatocytes and rates of serum markers of liver injury. Conclusions: 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. (c) 2017 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Sp. z o.o. All rights reserved.