The role of oxidative stress, apoptosis and altered TRPM2 channel activation in doxorubicin-induced liver injury; the protective effect of selenium

Aim: Doxorubicin (DOXR) is frequently used alone or as combination therapy in the treatment of various types of cancer. Although dose-dependent side effects are known, its effects on liver health are not fully known. This study aimed to investigate the role of the transient receptor potential melastatin-2 (TRPM2) channel in DOXR-treated rats using the TRPM-2 channel blocker N-(p-amylcinamoyl) anthranilic acid (ACA) and to investigate the protective effects of selenium (Se). Methods: Rats were allocated into six groups, each containing ten rats: control, DMSO, DOXR, DOXR + Se, DOXR + ACA, and DOXR + ACA + Se. Serum levels of AST, ALT, LDH, triglycerides, and total cholesterol were measured. Additionally, liver tissues were subjected to immunohistochemical tests for TRPM2 channel, 8-OHdG, and caspase-3 (Casp-3) expressions and also histopathological evaluation. Results: Serum AST, ALT, LDH, triglyceride and total cholesterol levels, as well as liver 8-OHdG, TRPM2 channel and Casp-3 expressions in the DOXR group were significantly higher than in the DOXR + Se, DOXR + ACA and DOXR + ACA + Se groups (p < 0.05). However, these parameters were significantly reduced in the Se and ACA-treated groups compared to the DOXR group (p < 0.05). Conclusions: The results suggest that simultaneous administration of Se or ACA with DOXR may provide an effective therapeutic approach to combat DOXR-induced hepatotoxicity.