Molecular and Genetic Medicine

DNA Oxidative Damage is Correlated with JNK Activation in Hepatocytes from Rats with Experimental Insulin Resistance

Abstract

Zagayko AL, Kravchenko GB, Krasilnikova OA and KochubeyJu I

Oxidative stress was improved as the main complication for a variety of pathological conditions. The present study was aimed to investigate the effect of insulin resistance development on c-Jun-N-terminal kinases (JNK) activity and DNA/RNA oxidative damage in rat’s liver under fructose rich diet. Total JNK, phosphorylated JNK-1 and JNK-2 ([pThr183/Tyr185] c-Jun N-terminal protein kinase (pJNK1/2), and 8-hydroxy-2`-deoxyguanosine (8-OHdG) amounts were measured in hepatocyte lysate. Glucose, insulin, free fatty acids, and triacylglicerols concentration and thiobarbituric acid reactive substances concentrations were measured in blood plasma. Catalase and superoxide dismutase activity, and thiobarbituric acid reactive substances (TBARS) were determined in liver homogenate. Fructose rich diet in rats provoked the insulin resistance that is accompanied by deep metabolic abnormalities detected in our study. These metabolic abnormalities induced by fructose overload are associated with an enhanced oxidative stress which appears to deregulate the JNK pathway. Consequently, accumulation of DNA/RNA oxidative damage stress marker – 8-OHdG– in hepatocytes positively correlates with JNK activity in the cells.