Resveratrol mitigates isoflurane-induced neuroapoptosis by inhibiting the activation of the Akt-regulated mitochondrial apoptotic signaling pathway.

The inhalation anesthetic, isoflurane, induces learning and memory impairment. Mitochondrial dysfunction and oxidative stress are thought to play important roles in isoflurane-induced neuroapoptosis. In this study, we treated neuronal cells with isoflurane for 6 h. We found that isoflurane induced the opening of mitochondrial permeability transition pores, increased the levels of reactive oxygen species and the activation of caspase‑3, and decreased the mitochondrial membrane potential and the intracellular calcium ion concentration. Resveratrol (RESV; trans-3,5,4'-trihydroxystilbene), a naturally occurring phytoalexin, is found at high concentrations in the skin of red grapes and red wine and has been demonstrated to have anti-infective, antioxidant and cardioprotective functions. Our findings demonstrated that the neuroprotective effects of RESV were independent on its direct radical scavenging properties. Following treatment of the cells with various concentrations of RESV, we found that RESV induced the expression of mitochondrial superoxide dismutase and catalase activity, and reduced mitochondrial oxidative stress and damage. The data from the present study demonstrate that RESV effectively protects neuronal cells from isoflurane-induced cytotoxicity by activating the Akt signaling pathway.