Melatonin Attenuates Ropivacaine-Induced Apoptosis by Inhibiting Excessive Mitophagy Through the Parkin / PINK1 Pathway in PC12 and HT22 Cells

Abstract Melatonin, as an endogenous circadian indoleamine, is secreted from the pineal gland and has extensive biological functions, including antioxidant, anti-inflammatory, anti-tumor and neuroprotective effects. Its neuroprotective effects make it to be a potential therapeutic for many nerve damages, but its effect on ropivacaine-induced neurotoxicity remains unclear. The aims of our research were to explore the impact and mechanism of melatonin on ropivacaine-induced neurotoxicity. Our results shown that melatonin pretreatment protected the cell viability, morphology, and apoptosis of PC12 and HT22 cells from ropivacaine, it also improved ropivacaine-induced mitochondrial dysfunction and it inhibited an increase of mitophagy levels by ropivacaine. In addition, our study also revealed that the increase of mitophagy levels could reduce the protective effect of melatonin on ropivacaine-induced apoptosis in PC12 and HT22 cells, but the inhibition of mitophagy could enhance this effect of melatonin. To further illustrate the mechanism of melatonin inhibited mitophagy, the expressions of Parkin and PINK1 were detected, and results shown that melatonin inhibited the activation of Parkin / PINK1 pathway. In conclusion, our results indicated that melatonin protected ropivacaine-induced apoptosis through suppressing excessive mitophagy by inhibiting the Parkin / PINK1 pathway. Melatonin may be a useful potential therapeutic agent against ropivacaine-induced neurotoxicity.