Protective effects of N-acetyl cysteine against paclitaxel-induced cardiotoxicity through modulation of transient receptor potential melastatin 2 channels

Abstract

Aim : In our study, we investigated the paclitaxel induced cardiotoxicity and alterations in Ca2+ influx, oxidative stress and apoptosis through transient receptor potential melastatin 2 (TRPM2) channels and modulator role of N-acetyl cysteine (NAC) in cardiomyocytes. Material and Methods : All cells were cultured at 37 degrees C. The cells were divided into seven main groups. Cells in the paclitaxel group were incubated with 2.5 mu M Paclitaxel for 12 hours and cells in the NAC+Paclitaxel group were incubated with 2.5 mu M Paclitaxel for 12 hours and then incubated with 10 mu M NAC for 24 hours. Intracellular free calcium concentration, reactive oxygen species (ROS) production measurements and cell viability analyses were done according to the study protocol. Results : Cytosolic calcium levels, apoptosis levels, intracellular ROS production levels were lower in paclitaxel+NAC group than in the paclitaxel group of cardiomyocytes. Also values were markedly lower in the paclitaxel+NAC+antranilic acid group when compared to the paclitaxel+ NAC group. Conclusion : We found that TRPM2 channels are overactivated during paclitaxel induced cardiotoxicity and NAC could show a cardioprotective effect through TRPM2 channel modulation.