Resveratrol protects neuronal cells from isoflurane-induced inflammation and oxidative stress-associated death by attenuating apoptosis via Akt/p38 MAPK signaling.

The aim of the present study was to determine whether resveratrol protects neuronal cells from inflammation and isoflurane-induced oxidative stress-associated death via attenuating apoptosis via Akt/p38 mitogen-activated protein kinase (MAPK) signaling. The PC12 rat pheochromocytoma cell line was treated with 2% isoflurane + 21% O2 + 5% CO2 for 6 h and pre-treated with resveratrol (0-1,000 µM) for 0, 24 or 48 h prior to isoflurane treatment. An MTT assay, flow cytometry and ELISA of tumor necrosis factor-α, interleukin-6, malondialdehyde and superoxide dismutase revealed that resveratrol reduced growth inhibition, restrained apoptosis and suppressed inflammation and oxidative stress induced by isoflurane in PC12 cells. Pretreatment with resveratrol effectively reduced caspase-3 activity and inducible nitric oxide synthase protein expression in isoflurane-induced PC12 cells. In addition, western blot analysis demonstrated that resveratrol treatment significantly attenuated isoflurane-induced decreases in the activated phosphorylated (p)-Akt/Akt ratio and increases in the p-p38/p38 MAPK protein ratio in PC12 cells. These findings indicated that resveratrol was able to protect neuronal cells from isoflurane-induced inflammation and oxidative stress-associated death by attenuating apoptosis via Akt/p38 MAPK signaling.