Curcumin Alleviates Ketamine-Induced Oxidative Stress and Apoptosis via Nrf2 Signaling Pathway in Rats’ Cerebral Cortex and Hippocampus

Aims: To study the protective effect of curcumin on nerve damage caused by ketamine anesthesia by Nrf2 signaling pathway. Methods: Rat cerebral cortex and hippocampus were collected for Nissl staining and immunohistochemistry to detect the number of neurons and the expressions of Caspase3, Bcl-2 and Bax. The optimal concentration of ketamine, curcumin and H2O2 on PC12 cells was determined by CCK-8 assay. Flow cytometry was used to detect the changes of reactive oxygen species and apoptosis rate in each group. Immunofluorescence was performed to observe whether Nrf2 entered the nucleus. Both tissues and cells were simultaneously subjected to RT-PCR and Western blotting detection. Oxidative stress levels were measured using a malondialdehyde (MDA) and superoxide dismutase (SOD) assay kit. Findings: Ketamine decreased the number of neurons in rats cortex and hippocampus. The expression of Bax and Caspase3 protein were up-regulated and the Bcl-2 was down-regulated in cortex and hippocampus. The cell viability of PC12 cells decreased. The content of MDA increased and the activity of SOD decreased in cortex, hippocampus and PC12 cells. Ketamine affected the expressions of some genes in Nrf2 signal pathway. Curcumin pretreatment could prevent the damage caused by ketamine. Conclusion: Curcumin could activate Nrf2 signaling pathway to alleviate oxidative stress and apoptosis, thus reducing ketamine-induced damage to cerebral cortex, hippocampus and PC12 cells during development. Our study provides a potential scheme for the safe use of anesthetics in clinic. Funding Information: This study was supported by the National Natural Science Foundation of China (31572580 and 31372491). Declaration of Interests: The authors declare that there are no conflicts of interest. Ethics Approval Statement: All experiments were carried out in accordance with the relevant laws of China and the animal welfare guidelines and experimental procedures of China. All procedures used in this study were approved by the animal protection and Utilization Committee of Northeast Agricultural University (SRM-11).