Investigation of the effect of selenium through TRPM2 cation channel in cadmium-induced in vivo neurotoxicity model

Neurotoxicity is a condition characterised by disorders of neuronal structure and function resulting from the accumulation of toxic substances in the central and peripheral nervous systems. Cadmium (Cd) is a heavy metal used in many industrial products. Numerous studies have shown that Cd exposure causes neurotoxic effects in living organisms. This study investigated whether selenium (Se) plays a protective role against cadmium-induced neurotoxicity in rat brain tissue due to its antioxidant and anti-inflammatory properties, and the role of the Transient Receptor Potential Melastatin 2 (TRPM2) channel in this mechanism. Forty male Wistar Albino rats were randomly divided into five groups (n=8): Control, CdCl₂, CdCl₂+Se, CdCl₂+2-APB, and CdCl₂+Se+2-APB. CdCl₂ (25 mg/kg) was administered intragastrically daily for 5 days according to group incubation, while Se (0.5 mg/kg) and the TRPM2 inhibitor 2-Aminoethoxydiphenylborate (2-APB) (3 mg/kg) were administered intraperitoneally. At the end of the study, total antioxidant level (TAS), total oxidant level (TOS), reactive oxygen species (ROS), poly (ADP-ribose) polymerase 1 (PARP-1), and TRPM2 channel levels were measured in the collected brain tissues using commercial ELISA kits. When the results were examined, TOS, ROS, PARP-1, and TRPM2 levels were found to be significantly higher in the CdCl₂ group compared to the other groups (p˂0.05). These parameters were higher in the CdCl₂+Se and CdCl₂+2-APB groups compared to the control group, but were significantly lower than in the CdCl₂ group (p˂0.05). In the CdCl₂+Se+2-APB group, these parameters were found to be at the lowest level among all CdCl₂-containing groups (p˂0.05). On the other hand, while the CdCl₂ group had the lowest TAS level, the application of Se and 2-APB significantly increased this level, and the highest TAS level was observed in the CdCl₂+Se+2-APB group compared to the other Cd groups (p˂0.05). As a result, Cd was found to activate a pathway of significant oxidative stress and TRPM2 channel activation in rat brain tissue and to increase channel expression. It was understood that Se and 2-APB treatment and TRPM2 channel inactivation significantly reduced CdCl₂-induced neurotoxicity.