Role of Antioxidant Vitamins on the Expression of HNF-1 Alpha Sterol Regulatory Element Binding Protein 1-C in PCB-Induced Experimental Diabetic Rats

Abstract

Introduction: PCB ( polychlorinated biphenyl ) is one among the environmental pollutants or toxicants and in addition to that it is also one of the neurologically toxic compounds. PCB functions by inducing the production of free radicals which in turn leads to the formation of oxidative stress. In the human body, antioxidants are classified into two groups based on the source of availability into endogenous and exogenous antioxidants. Vitamin C and vitamin E are well-known antioxidants . Vitamin C (ascorbic acid) is a water soluble vitamin, vitamin E (tocopherol) is a fat soluble vitamin. Vitamin inhabit the membrane disintegration effects of ROS reactive oxygen species which is induced by lipid peroxidation. Vitamin C is found in plasma and it helps in the production of collagen synthesis.

Materials and Methods: Adult male albino rats were divided into 3 groups. Group I: served as vehicle control (corn oil alone); Group II: Control rats were injected intraperitoneally daily with  PCB (Aroclor 1254) at a dose of 2mg/k.b.wt , for 30 days to induce diabetes; Group III: PCB induced rats treated with vitamins E (50 mg/kg body weight) and C (100 mg/kg body weight), once daily through gastric intubation for 30 days. On completion of treatment, animals were anesthetized, blood was collected, sera were separated, gastrocnemius muscle was dissected out and subjected to assessment of gene expression analysis.  Fasting blood glucose, serum insulin levels were measured in the serum whereas, HNF-1 alpha mRNA and SREBP-1c proteins were measured in the skeletal muscle using Real Time-PCR analysis using gene specific primers and ELISA methods. The data were statistically analyzed using One-Way-ANOVA followed by Duncan’s multiple range test were used to check the statistical significance and considered at the levels of p<0.05.

Results and Discussion: PCB-induced animals showed a significant increase (p<0.05) in both fasting blood glucose (FBG) and fasting serum insulin levels compared to control rats. Vitamin supplementations (Vit C and E) effectively reduced the FBG and serum insulin levels near to that of the control animals. mRNA expression of SREBP1-c was also found to be significantly increased in PCB-induced rats while HNF-1 alpha mRNA levels were found to be reduced in PCB-exposed rats. Antioxidant vitamins treatment normalized the gene expression levels.

Conclusion: Our study for the first time providing an evidence that Vitamin C and E have the potency in reducing hyperglycemia and hyperinsulinemia by modulating the expression of HNF-1 alpha and SREBP1-c in the PCB-induced diabetic gastrocnemius muscle. Therefore, Vitamin C and E could be a promising drug candidate for the management of type-2 diabetes.