Prophylactic supplement with melatonin prevented the brain injury after cardiac arrest in rats through SIRT3/CypD activation and PINK1/Parkin induced mitophagy

Abstract

AbstractBackground Prophylactic pharmacotherapy for health care in patients with high risk of cardiac arrest (CA) is an elusive and less explored strategy. Melatonin has possibilities used as a daily nutraceutical to trigger the cellular adaptation. We sought to find the effects of long-term daily prophylactic supplement with melatonin on the victim of CA. Methods Rats were divided into sham, CA, and melatonin + CA (Mel + CA) groups. The rats in the Mel + CA group received daily IP injection of melatonin 100 mg/kg for 14 days. CA was induced by 8 mins asphyxia and followed by manual CPR. The endpoint was 24 h after resuscitation. Survival, neurological outcome, and hippocampal mitochondrial integrity, dynamics and function were assessed. Results Survival was significantly higher in the Mel + CA group than the CA group (81% vs. 42%,P = 0.04). Compared to the CA group, neurological damage in the CA1 region and the expression of cytochrome c, cleaved caspase-3 and caspase-9 in the Mel + CA group were decreased (P < 0.05). Mitochondrial function and integrity were protected in the Mel + CA group compared to the CA group, according to the results of mitochondrial swelling, ΔΨm, ROS production, oxygen consumption rate, and respiratory control rate (P < 0.05). Melatonin increased SIRT3 and downregulated acetylated CypD. The mitochondrial dynamics and autophagy were improved in the Mel + CA group (P < 0.05). Conclusions Long-term daily prophylactic supplement with melatonin buy the time from brain injury after CA.