Melatonin protected against myocardial infarction injury in rats through a Sirt6-dependent antioxidant pathway

Abstract

Background. The Sirt6, one of the members of the sirtuin family, has been regarded as a key factor in the pathogenesis of myocardial infarction (MI) through its antioxidant defense mechanisms. A previous study reported that melatonin is an antioxidant drug that can act as an agent for cardioprotection in cardiac ischemia-reperfusion (I/R) injury. However, whether melatonin could protect against cardiac remodeling after myocardial injury via the Sirt6-dependent antioxidant pathway remains unknown.Objectives. To explore the protective effects and the potential mechanisms of melatonin on MI-induced injury in rats. Materials and methods.A cardiac remodeling model was established through left coronary artery ligation surgery. The dose of melatonin was 10 mg/kg body weight. Four weeks after the treatment for 7 successive days, the infarct size and hemodynamic parameters were evaluated. The relative mRNA level and protein level of Sirt6 were also determined. Finally, the levels of oxidative stress, including reactive oxygen species (ROS) and superoxide dismutase (SOD), were measured, and the expression of nitric oxide (NO), inducible nitric oxide synthase (iNOS), endothelial nitric oxide synthase (eNOS) and their corresponding phosphorylation were evaluated.Results. After the treatment with melatonin, infarct size, the left ventricular end-diastolic diameter (LVEDd), and left ventricular end-systolic diameter (LVEDd) and minimum first derivative of developed pressure (min dP/dt) decreased, while left ventricular ejection fraction (LVEF), left ventricular fractional shortening (LVFS) and maximum first derivative of developed pressure (max dP/dt) increased in the melatonin-MI (MM) group compared to the placebo-MI (PM) group. Furthermore, the expressions of Sirt6, both in mRNA and protein level, were significantly increased in the MM group treated with melatonin, as compared to the melatonin-control (MC) group treated with melatonin. In addition, melatonin enhanced SOD activity and reduced ROS levels. At the same time, we observed that the eNOS/NO signaling pathways were activated.Conclusions. Melatonin improved cardiac function through the Sirt6-dependent antioxidant pathway in MI rats.

The role of complement C3 in the outcome of regional myocardial infarction

“…It is of note that in our study, cardiac function of WT mice had sharply deteriorated at 4 weeks after ischemia, which is in agreement with others using rodent models of IRI [ [54] , [55] , [56] ]. One possible explanation is that cardiac function was initially restored by reperfusion, but cardiac fibrosis gradually evolved and reached the threshold at 4 weeks after ischemia.…”

Traumatic Brain Injury, Sleep, and Melatonin—Intrinsic Changes with Therapeutic Potential

“…Intraperitoneal melatonin administration in rats after a surgically induced myocardial infarction (MI) was associated with an increased plasma level of Sirt6 , a stress response protein involved in metabolic pathways affecting DNA repair, ATP production, and inflammation. Evidence shows melatonin may significantly increases Sirt6 mRNA transcription while reducing the levels of iNOS and phosphorylated iNOS after ischemic insult [ 158 , 159 ]. While one study found decreased myocardial infarct size and ROS levels following melatonin administration, these findings were not statistically significant [ 159 ].…”

“…Evidence shows melatonin may significantly increases Sirt6 mRNA transcription while reducing the levels of iNOS and phosphorylated iNOS after ischemic insult [ 158 , 159 ]. While one study found decreased myocardial infarct size and ROS levels following melatonin administration, these findings were not statistically significant [ 159 ].…”

The role of mammalian Sirtuin 6 in cardiovascular diseases and diabetes mellitus

“…For example, myocardial infarction alters the transcriptional activity of Sirt6 gene promoter and influences Sirt6 protein expression levels ( Wang L. et al, 2016 ). Also, Wang Y. et al, 2022 found that melatonin attenuates myocardial infarction and preserves cardiac function by activating Sirt6-dependent antioxidant pathway. Furthermore, it is reported that metformin therapy mitigates cardiovascular outcomes by improving Sirt6 levels in acute myocardial infarction-prediabetes (AMI-PDM) patients ( Sardu et al, 2021 ).…”