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.
Department of Anaesthesiology, the First Hospital of China Medical University, Shenyang, Liaoning 110001, PR China. baitao720418@163.com
Tao
T
Bai
Dao-Song
DS
Dong
Ling
L
Pei
D018685:Anesthetics, Inhalation / Q000009:adverse effects; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D053181:Caspase 8 / Q000235:genetics / Q000378:metabolism; D053453:Caspase 9 / Q000235:genetics / Q000378:metabolism; D020552:Comet Assay; D004249:DNA Damage / Q000187:drug effects; D020287:In Situ Nick-End Labeling; D007530:Isoflurane / Q000009:adverse effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism; D000083162:Mitochondrial Permeability Transition Pore; D009474:Neurons / Q000166:cytology / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D000077185:Resveratrol; D015398:Signal Transduction; D013267:Stilbenes / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism
D018685:Anesthetics, Inhalation; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D013267:Stilbenes; D007530:Isoflurane; D013482:Superoxide Dismutase; D051057:Proto-Oncogene Proteins c-akt; C505409:Casp3 protein, mouse; C505526:Casp8 protein, mouse; C506434:Casp9 protein, mouse; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D000077185:Resveratrol