Coenzyme Q10 Mitigates Hepatocellular Damage in Fructose-Fed Streptozotocin-Induced Diabetic Rats via Decrease in Oxidative-stress, Inflammation, and Modulation of Key Pathways

Abstract

Coenzyme Q10 (CoQ10) has been examined in several diabetic and/or insulin-resistant models; however, a thorough explanation of its precise mechanisms is still lacking. This study investigated the protective effect of CoQ10 in fructose-fed streptozotocin-induced diabetic rats via redox regulation and modulation of some key pathways. Male Wistar rats were pre-fed with 20% (w/v) fructose water for one week and thereafter injected with streptozotocin intraperitoneal. The animals were treated with CoQ10 for two weeks after confirmation of diabetes. Thereafter, they were euthanized, blood and liver samples were collected for biochemical and histopathological studies.  Glycemic indices, carbohydrate metabolizing enzymes (both in vitro and in vivo), liver biomarkers, oxidative stress and inflammatory markers, and redox status were investigated. The mRNA expression level of GSK-3β, GLUT-2, and some inflammatory genes was also assessed. The results revealed that CoQ10 significantly modulates the glycemic indices, carbohydrate metabolizing enzymes, and mitigates the detrimental effect of the STZ-induced diabetes in the liver by lowering the concentrations of the oxidative stress markers and improving the activity of the endogenous antioxidant enzymes and the concentration of the anti-inflammatory cytokine. Administration of CoQ10 downregulated GSK-3β, TNF-α, and NF-kB mRNA expression levels, and upregulated GLUT-2 and IL-10 mRNA expression levels. CoQ10 protected the hepatic tissue from hyperglycemia and oxidative stress resulting from STZ-induced diabetes and also modulated the expression of genes implicated in the insulin signaling pathway. CoQ10 protects by alleviating the impairment of insulin signaling in diabetic rats and could be an effective therapeutic agent for the management of diabetes.