Isoflurane preconditioning attenuates OGD/R‐induced cardiomyocyte cytotoxicity by regulating the miR‐210/BNIP3 axis.

Zhang, Dongbo; Wu, Qiaoling; Liu, Feifei; Shen, Tu; Dai, Siqi

Isoflurane, a commonly used inhaled anesthetic, has been found to have a cardioprotective effect. However, the precise mechanisms have not been fully elucidated. Here, we found that isoflurane preconditioning enhanced OGD/R‐induced upregulation of miR‐210, a hypoxia‐responsive miRNA, in AC16 human myocardial cells. To further test the roles of miR‐210 in regulating the effects of isoflurane preconditioning on OGD/R‐induced cardiomyocyte injury, AC16 cells were transfected with anti‐miR‐210 or control anti‐miRNA. Results showed that isoflurane preconditioning attenuated OGD/R‐induced cardiomyocyte cytotoxicity (as assessed by cell viability, LDH and CK‐MB levels), which could be reversed by anti‐miR‐210. Isoflurane preconditioning also prevented OGD/R‐induced increase in apoptotic rate, caspase‐3 and caspase‐9 activities, and Bax level and decrease in Bcl‐2 expression level, while anti‐miR‐210 blocked these effects. We also found that anti‐miR‐210 prevented the inhibitory effects of isoflurane preconditioning on OGD/R‐induced decrease in adenosine triphosphate content; mitochondrial volume; citrate synthase activity; complex I, II, and IV activities; and p‐DRP1 and MFN2 expression. Besides, the expression of BNIP3, a reported direct target of miR‐210, was significantly decreased under hypoxia condition and could be regulated by isoflurane preconditioning. In addition, BNIP3 knockdown attenuated the effects of miR‐210 silencing on the cytoprotection of isoflurane preconditioning. These findings suggested that isoflurane preconditioning exerted protective effects against OGD/R‐induced cardiac cytotoxicity by regulating the miR‐210/BNIP3 axis. Isoflurane preconditioning elicited cardioprotection against OGD/R‐induced cardiomyocyte injury via maintaining mitochondrial function by regulating the miR‐210/BNIP3 axis. Our study provided new evidence for the underlying molecular mechanisms of protective effects of isoflurane preconditioning against OGD/R‐induced injury in cardiomyocytes.

CITRATE synthase; ADENOSINE triphosphate; CYTOTOXINS; ISOFLURANE; CELL survival

Journal of Applied Toxicology, 2024, Vol 44, Issue 11, p1761

0260-437X

Academic Journal

10.1002/jat.4674