Melatonin ameliorates docetaxel-induced mitochondrial oxidative toxicity and cytokine generation in the laryngo-tracheal epithelial cell

摘要

A protective action of melatonin(MELAT)on docetaxel(DCT)-induced inflammation,apoptosis,and reactive free oxygen radical(fROS)generation values via blocking of TRPM2 calcium-permeable channel was investigated in different cells except for laryngo-tracheal epithelial(LT-Epi)cells.Hence,the protective action ofMELAT on DCT-induced oxidative toxicity and inflammation in LT-Epi tissue and cells of mice were investigated in the current study.MELAT treatment ameliorated DCTinduced mitochondrial ROS in the LT-Epi cells by reducing the generation of fROS(cytosolic and mitochondrial),lipid peroxidation,and depolarization of the mitochondrial membrane,while increasing reduced glutathione(GSH),GSH peroxidase,and total antioxidant status.In addition,DCT-induced increases of cytokine(IL-1β,IL-6,and TNF-α)generations were also diminished in the LT-Epi tissue by MELAT treatment.Furthermore,MELAT treatment increased viability and count of the cells followed by decreasing levels of cell death,caspase-3,and-9.The TRPM2 activity was also reduced by MELAT and TRPM2 channel blocker(ACA)treatments.In conclusion,MELAT modulated the increase of DCT-induced LT-Epi cell death by inhibiting mitochondrial oxidative stress and TRPM2 channel activity.Hence,DCTcaused side cell death,oxidant,and inflammatory actions in the LT-Epi were diminished via the treatment of MELAT.