Ketamine attenuates hypoxia-induced cell death and oxidative toxicity via inhibition of the TRPM2 channel in neuronal cells

Authors : Haci Ömer OSMANLIOĞLU

Pages : 1095-1104

View : 36 | Download : 25

Publication Date : 2022-12-30

Article Type : Research Paper

Abstract :Ketamine insert ignore into journalissuearticles values(KET); is a pediatric anesthetic agent, and it acts antioxidant action via the inhibition of Ca2+ influx and N-methyl-D-aspartate insert ignore into journalissuearticles values(NMDA); receptors, apoptosis, intracellular insert ignore into journalissuearticles values(iROS);, and mitochondrial reactive oxygen species insert ignore into journalissuearticles values(mROS); productions. Hypoxia insert ignore into journalissuearticles values(HYP);-induced oxidative stress activates the TRPM2 channel, although 2-aminoethoxydiphenyl borate insert ignore into journalissuearticles values(2APB); inhibits it. The treatment of KET inhibits HYP-induced oxidative stress and apoptosis in neuronal cells, although conflicting information is also present. We aimed to the modulator role of KET on the HYP-mediated oxidative cytotoxicity and apoptosis in the SH-SY5Y neuronal cells via modulating the TRPM2 signaling pathways. We induced five primary groups in the SH-SY5Y cells: Control, KET insert ignore into journalissuearticles values(0.3 mM for 24h);, HYP insert ignore into journalissuearticles values(CoCl2 and 200 M for 24h);, HYP+KET, and HYP+2APB. The amounts of apoptosis, cell death insert ignore into journalissuearticles values(propidium iodide positive cell number);, oxidants insert ignore into journalissuearticles values(mROS and iROS);, and cytosolic free Ca2+ were increased via TRPM2 stimulation by the incubation of HYP, although their amounts were diminished by KET and 2APB. In conclusion, the treatment of KET attenuated the HYP-induced oxidative stress and neuronal death levels via TRPM2 inhibition in the SH-SY5Y neuronal cells. The KET may be considered as a potential therapeutic way to HYP-induced oxidative neuronal injury.
Keywords : Hypoxia, Ketamine, Neuronal injury, Oxidative stress, TRPM2 channel