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

Background: 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.