Glutathione and TRPM2 Inhibition Reduce Amyloid‐Beta and Lipopolysaccharide‐Induced Apoptosis, Inflammation, and Oxidative Stress in Microglial Cells

Microglia cells impacted by inflammation and Alzheimer's disease produce toxic reactive oxygen species (ROS), emit signaling molecules, and death as a result of microglia being active due to excessive Ca²⁺ entering the cells. The TRPM2 channel plays a crucial role in Ca²⁺ permeability, inflammation, ROS, and apoptosis changes in the BV2 microglia cells, while glutathione (GSH) treatment reduces the changes through TRPM2 inhibition. However, the effect of TRPM2 inhibitors and GSH treatment on oxidative stress, inflammation, and apoptotic values in BV2 microglia cells activated with LPS and amyloid-beta (Aβ) has not been investigated yet. The study aimed to assess the effects of TRPM2 inhibition and GSH treatment on the values in BV2 cells activated with LPS and Aβ. BV2 cells were divided into five groups: control (CNT), LPS, Aβ, Aβ + LPS, and Aβ + LPS + GSH. Increased levels of inflammation biomarkers (TNF-α, IL-1β, and IL-6), intracellular Ca²⁺ level, cytosolic ROS, mitochondrial membrane dysfunction, cell death, apoptosis, caspases (caspase-3, -8, and -9), and TRPM2 current density were observed in the cells stimulated with LPS and Aβ. These values increased more when LPS and Aβ were incubated together. However, these apoptotic, inflammatory, and oxidant levels decreased in cells treated with GSH and TRPM2 blockers. In conclusion, the involvement of TRPM2 stimulation was demonstrated on Aβ and LPS-induced Ca²⁺ entry, oxidative stress, inflammation, and apoptosis parameters in microglia cells. TRPM2 inhibition by GSH treatment seems to be a potential source for the prevention of Aβ and LPS-induced oxidative stress, apoptosis, and inflammation.