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

Abstract

Ketamine (KET) is a pediatric anesthetic agent, and it acts antioxidant action via the inhibition of Ca2+ influx and N-methyl-D-aspartate (NMDA) receptors, apoptosis, intracellular (iROS), and mitochondrial reactive oxygen species (mROS) productions. Hypoxia (HYP)-induced oxidative stress activates the TRPM2 channel, although 2-aminoethoxydiphenyl borate (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 (0.3 mM for 24h), HYP (CoCl2 and 200 M for 24h), HYP+KET, and HYP+2APB. The amounts of apoptosis, cell death (propidium iodide positive cell number), oxidants (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.