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Graphical abstract

In the current study, it was found that high fat diet (60% of total kCal) (H) or/and isoproterenol (I) exacerbated oxidative stress and caused myocardial damage. This was indicated by increased levels of LPO, PCO, abnormal mitochondria and altered activities of metabolic as well as antioxidant enzymes in myocardium of rats. Melatonin at different doses (10, 20 and 40 mg/kg) effectively protected against myocardial damage induced by H or/and I and preserved all of these altered parameters. Morphological analyses showed that combination of H and I treatment led to the extensive myofibril disintegration and neutrophil infiltration. Melatonin at the dose of 40 mg/kg almost completely prevented these pathological alterations. The mechanistical studies have uncovered that the protective effects of melatonin on the myocardial damage induced by H and I are attributed to its direct and indirect antioxidative capacity, i.e., it directly scavenges free radicals and also regulates the gene expression of antioxidant enzymes. Collectively, based on the evidences gathered from the current study, it will not be unwise to suggest that melatonin can serve as an ideal therapeutic agent for those cardiovascular diseases caused by oxidative stress.

High fat diet (HFD) has been implicated as an independent risk factor for cardiovascular diseases since the second half of the last century. The HFD causes various pathogeneses and progressions of cardiovascular diseases. The oxidative stress and pro-inflammatory reactions induced by the HFD are probably the major risk factors of myocardial damage. In this review we highlight the roles of different dietary fats on cardiovascular diseases and the protective effects of melatonin as a potent antioxidant and anti-inflammation molecule on the pathology induced by HFD. The focus will be given to the molecular mechanisms. The protective effects of melatonin on HFD induced myocardial damage are mediated by multiple pathways. These include that melatonin suppresses the oxidative stress, preserves the normal fat and glucose metabolisms and reduces the pro-inflammatory reactions. Melatonin downregulates the expressions of pro-inflammatory genes of TLR4, NF-κB and NLRP3-Caspase1 but upregulates the expressions of anti-inflammatory genes of Sirt3, CTRP3 and RISK. All of these render melatonin as a powerful protector against cardiovascular diseases caused by the HFD. This review suggests that melatonin can be used as a therapeutic agent in this specific condition.