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

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.

An extract of Hypericum perforatum induces wound healing through inhibitions of Ca^(2+) mobilizations,mitochondrial oxidative stress and cell death in epithelial cells:Involvement of TRPM2 channels

The wound is induced by several mechanical and metabolic factors.In the etiology of the wound recovery,excessive oxidative stress,calcium ion(Ca^(2+))influx,and apoptosis have important roles.Ca^(2+)-permeable TRPM2 channel is activated by oxidative stress.Protective roles of Hypericum perforatum extract(HP)on the mechanical nerve injury-induced apoptosis and oxidative toxicity through regulation of TRPM2 in the experimental animals were recently reported.The potential protective roles in HP treatment were evaluated on the TRPM2-mediated cellular oxidative toxicity in the renal epithelium(MPK)cells.The cells were divided into three groups as control,wound,and wound+HP treatment(75μM for 72 h).Wound diameters were more importantly decreased in the wound+HP group than in the wound group.In addition,the results of laser confocal microscopy analyses indicated protective roles of HP and TRPM2 antagonists(N-(p-Amylcinnamoyl)anthranilic acid and 2-aminoethyl diphenylborinate)against the wound-induced increase of Ca^(2+) influx and mitochondrial ROS production.The wound-induced increase of early(annexin V-FITC)apoptosis and late(propidium iodide)apoptosis were also decreased in the cells by the HP treatment.In conclusion,HP treatment acted protective effects against wound-mediated oxidative cell toxicity and apoptosis through TRPM2 inhibition.These effects may be attributed to their potent antioxidant effect.