Dietary flaxseed oil and fish oil modulates expression of antioxidant and inflammatory genes with alleviation of protein glycation status and inflammation in liver of streptozotocin nicotinamide induced diabetic rats

Beneficial effects of dietary flaxseed oil or fish oil on streptozotocin nicotinamide induced diabetic rats were investigated. Rats were divided into three diabetic and three non diabetic groups and received control, flaxseed oil or fish oil diets (10 percent  w/w). Both diets reduced blood glucose, TBARS and hepatic NO. The extent of glycation measured in terms of glycated albumin and hemoglobin was reduced significantly with both diets. Flaxseed oil diet up regulated hepatic catalase (CAT) (activity and expression), superoxide dismutase (SOD) (activity and expression) and glutathione peroxidase (GPx) expression. Fish oil diet Up regulated hepatic CAT (activity and expression), paraoxonase1 (PON1) expression and down-regulated heme oxygenase1 (HO1) expression. Furthermore, both diets down-regulated the expression of hepatic inflammatory genes TNFa, IL6, MCP1, INFc and NFjB. These results were supported by histopathological observations which showed better tissue preservation in both the diets. Thus, both the diets proved to be beneficial in preventing tissue injury and alleviating diabetic insults in the livers of STZ NIC diabetic rats. (Author abstract)

Type 2 diabetes mellitus (T2DM) is a complex endocrine metabolic disorder associated with several complications. There is considerable evidence suggesting that oxidative stress and inflammation are major factors for the development of T2DM. There is a higher risk of liver dysfunction in T2DM. Oxidative stress in diabetes is developed due to oxidation of glucose and over-glycation of proteins, including hemoglobin, which lead to production of reactive oxygen species (ROS). The primary defense against oxidative stress is regulated by antioxidant enzymes such as superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT). The enzymatic activity of these antioxidants is reduced under the diabetic condition. Secondly, over-expression of pro inflammatory cytokines, such as tumor necrosis factor alpha (TNFa), interleukin6 (IL6) and monocyte chemoattractant protein 1 (MCP1) is also involved in the pathogenesis of T2DM. Hepatocytes actively respond to these pro inflammatory cytokines and promptly translate the signals into increased expression of pro inflammatory genes leading to tissue injury. In diabetes, over glycation of proteins such as hemoglobin and albumin leads to the formation of ‘‘advanced glycation end products’’ (AGEs).  It appears that increased oxidative stress and inflammatory insults may be ameliorated by the consumption of n3 fatty acids. The objective was to evaluate the effects of flaxseed oil and fish oil diets on the oxidative stress and inflammatory changes in the livers of streptozotocin nicotinamide (STZ NIC) rats. In this study, blood glucose levels were marginally reduced in rats receiving the flaxseed oil diet or the fish oil diet. However, both dietary flaxseed oil or fish oil were able to lower the levels of glycated proteins as compared to levels for diabetic rats, thus averting further increases in oxidative stress and inflammation . The flaxseed oil diet also lowered glycated albumin levels in control rats. Dietary flaxseed oil or fish oil significantly decreased the levels of hepatic TBARS and plasma TBARS as well as hepatic nitric oxide concentrations in diabetic rats. The flaxseed oil diet increased both hepatic-SOD and hepatic-CAT activities, while the fish oil diet increased the hepatic activity of CAT enzyme. The flaxseed oil or fish oil diets showed significant down-regulation of transcripts of TNFa, IL6, MCP1, INFc and NFjB (p65 subunit) in diabetic rat liver. The histopathological parameters in this study revealed lesser degeneration of hepatocytes in rats receiving the flaxseed oil or fish oil diet as compared with diabetic control rats. This could be attributed to lowering the expression of inflammatory genes and reduction in oxidative stress in the liver.

A flaxseed oil diet or fish oil diet showed significantly reduced levels of blood glucose, hepatic TBARS, plasma TBARS and HbA1c. These diets also significantly lowered hepatic expression of inflammatory biomarkers. Both the diets revealed comparable effects on up regulation of hepatic CAT-gene expression and alleviating the pathological changes in liver histology. The flaxseed oil diet was better at increasing hepatic activities of SOD, CAT and hepatic gene expression of SOD and GPx. The flaxseed oil diet also proved to be better at reducing hepatic nitric oxide concentrations. The n3 diets proved to be beneficial in protecting against injury and potential complications in liver tissue of STZ NIC induced diabetic rats. (Editors comments)