Naringenin protects cardiac hypercholesterolemia-induced oxidative stress and subsequent necroptosis in rats

Abstract Background In earlier studies, the supplementation of the natural compound Naringenin (NGEN), improved the liver oxidative and inflammatory status, which indicates its direct effect via inhibition of the nuclear factor κB pathway on high cholesterol-induced hepatic damages. In this regard, the present study highlights the mechanisms associated with the protective efficacy of NGEN in the heart tissue of hypercholesterolemic diet rats. Results The animals exposed to a high cholesterol diet (HCD) for 90 days exhibited a significant increase in the levels of serum lactate dehydrogenase (LDH) and creatine kinase (CK) activities, nitric oxide (NO) levels, protein and lipid oxidative markers and cardiac lipids profile. Moreover, hypercholesterolemia decreased the levels of enzymatic and non enzymatic antioxidants associated with mitochondrial dysfunctions as proved by the decrease in the mitochondrial complexes in comparison to controls. Importantly, cholesterol-feeding significantly increased myocardial reactive oxygen species (ROS) and nuclear DNA damage and led to the activation of gene expression of the tumor necrosis factor-α (TNF-α) and receptor-interacting protein kinase 3 (RIP3) mRNA that contributed to the elucidation of cholesterol-induced necroptosis, a recently described type of programmed necrosis, in the cardiac tissue. Conclusions Our results show that the co-administration of NGEN (50 mg/kg/bw) in HCD rats improved all the altered parameters and provided insight into a possible molecular mechanism underlying NGEN suppression of necroptosis pathway in the heart.