Aging and Hyperglycemia Intensify Dyslipidemia-Induced Oxidative Stress and Inflammation in Rats: Assessment of Restorative Potentials of ALA and EPA + DHA

Effect of aging and hyperglycemia on oxidative stress (OS) and inflammation in dyslipidemic conditions has not been elucidated. Hence, in this study, we assessed the implications of aging, hyperglycemia, and also the dietary effect of n-3 fatty acids (α-linolenic acid (ALA) and eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA)) on OS and inflammation in dyslipidemic rats. Dyslipidemia was induced in young and aged rats by feeding high-fat lard (HFL) diet. Diabetes was induced in young dyslipidemic rats by administering streptozotocin 30 days after the induction of dyslipidemia. Experimental groups received diets containing canola oil (HF + CNO) and fish oil (HF + FO) as a source of ALA and EPA + DHA respectively. After 60 days of feeding rats with their respective diets, OS and inflammatory markers in serum were assessed. Dyslipidemia caused significant (p < 0.05) increase in OS (lipid peroxidation, nitric oxide, and protein carbonyl), pro-inflammatory cytokine (CRP, IL-1β, MCP-1, and TNF-α), and eicosanoid (PGE₂, LTB₄, and LTC₄) level in serum of both young and aged rats. Aged dyslipidemic rats presented significantly (p < 0.05) higher level of these markers compared to young dyslipidemic rats. Hyperglycemia onset further augmented OS and inflammatory markers in young dyslipidemic rats significantly (p < 0.05). Administration of n-3 fatty acids downregulated the serum markers of OS and inflammation in all the three experimental models. Thus, aging and hyperglycemia onset intensified dyslipidemia-induced OS and inflammation. Dietary preformed EPA + DHA presented larger restorative potentials than precursor ALA in countering OS and inflammation in all the three experimental models.