Propofol's Neuroprotective Effect Against Cisplatin-Induced Oxidative Neurotoxicity Via Suppression of the TRPM2 Cation Channel

Objective: Cisplatin (CSP) exhibits strong oxidant and apoptotic effects in tumors, but it also causes adverse neurodegenerative effects by stimulating the TRPM2 cation channel. By regulating mitochondrial reactive free oxygen species (ROS) and excessive Ca2+ entry-mediated apoptosis, propofol (PRPF) exhibits antioxidant and neuroprotective properties. However, the action of the TRPM2 in these productions in human SH-SY5Y neuronal cells has not yet been determined. In SH-SY5Y, I investigated the protective effects of PRPF by modifying TRPM2, which affects CSP-induced neuronal mitochondrial function and death. Materials and Methods: I generated five main groups in the SH-SY5Y as control, PRPF (200 mM for 24h), CSP (25 mM for 24h), CSP + PRPF, and CSP + TRPM2 channel antagonists (25 mM ACA and 100 mM 2APB). Results: Through TRPM2 stimulation, the incubation with CSP increased the amounts of apoptosis, caspase -3, caspase -9, cell death percentage, ROS, mitochondrial hyperpolarization, TRPM2 current densities, and intracellular free Ca2+. However, the incubation of PRPF through the inhibition of TRPM2 decreased the amounts of these processes. Conclusions: PRPF treatment via TRPM2 suppression decreased the levels of mitochondrial oxidative stress and neuronal death caused by CSP. One effective therapy option for CSP-induced mitochondrial oxidative neuronal damage is the PRPF.