Antioxidative effects of diallyl trisulfide on hydrogen peroxide-induced cytotoxicity through regulation of nuclear factor-E2-related factor-mediated thioredoxin reductase 1 expression in C2C12 skeletal muscle myoblast cells

Abstract

Diallyl trisulfide (DATS) is one of the major sulfur-containing compounds in garlic oil. In this study, we analyzed the effects of DATS against hydrogen peroxide (H2O2)-induced oxidative stress in C2C12 myoblasts. DATS preconditioning significantly attenuated H2O2-induced growth inhibition and DNA damage, as well as apoptosis by decreasing the generation of ROS. Treatment with DATS alone effectively upregulated the expression of nuclear factor-erythroid 2-related factor 2 (Nrf2) and thioredoxin reductase 1 (TrxR1), which was associated with the increased phosphorylation of Nrf2. However, the protective effects of DATS against H2O2-induced growth reduction and ROS accumulation were significantly abolished by auranofin, an inhibitor of TrxR activity. Moreover, DATS-mediated phosphorylation of Nrf2 and induction of TrxR1 were markedly reduced by genetic silencing of Nrf2. DATS treatment also induced the phosphorylation extracellular signal-regulating kinase (ERK), and analysis using specific inhibitors of cellular signaling pathways demonstrated that only ERK activation was involved in Nrf2 phosphorylation and TrxR1 induction. In addition, the cytoprotective potentials were abrogated in C2C12 cells pretreated with an ERK specific inhibitor. The results demonstrate that DATS protects against oxidative stress-induced DNA damage and apoptosis in C2C12 cells in part through the activation of Nrf2-mediated TrxR1 induction via the ERK signaling pathway.

Activation of the Nrf2/HO-1 signaling pathway contributes to the protective effects of platycodin D against oxidative stress-induced DNA damage and apoptosis in C2C12 myoblasts

“…Consistent with these results, the reduced apoptosis and increased cell viability by pretreatment with platycodin D in the presence of H 2 O 2 were significantly reversed in Nrf2 siRNA-transfected cells. These results well support previous findings that activating Nrf2/HO-1 signaling in C2C12 myoblasts could initiate a protective mechanism for initiating an intrinsic apoptosis pathway following oxidative stress-mediated mitochondrial dysfunction and DNA damage (Kang et al 2015(Kang et al , 2017Choi 2016;Han et al 2017).…”

“…In addition, various natural products have been reported to have antioxidant properties through the activation of the Nrf2/HO-1 signaling pathway to protect against apoptosis caused by oxidative injury in myoblasts (Kang et al 2015(Kang et al , 2017Choi 2016;Han et al 2017). In present study, platycodin D up-regulated the expression of Nrf2 and p-Nrf2 in the absence of H 2 O 2 , which is due to antioxidant activity of platycodin D. In addition, I explored the effect of platycodin D on the expression of Nrf2, and found that the expression of p-Nrf2 was markedly upregulated by platycodin D in the presence of H 2 O 2 .…”

Evaluation of Antioxidant Activity of Spice-Derived Phytochemicals Using Zebrafish

“…Diallyl trisulfide showed protective effects against H 2 O 2 toxicity at concentrations of 12.5 and 25 µM, but against NaAsO 2 toxicity it induced lethality, even at 5 µM, suggesting the cotoxicity of diallyl trisulfide and arsenite. Previous reports showed that diallyl trisulfide not only ameliorates H 2 O 2 toxicity in C2C12 skeletal muscle myoblast cells in a Nrf2-dependent manner [45], but also protects the rat liver from arsenic acid damage [46]. It is not known whether this discrepancy is due to the difference in arsenic forms, tissues/cells or species.…”

Functional Application of Sulfur-Containing Spice Compounds

“…When Nrf2 is bound to an antioxidant response element (ARE) in the promoter region of genes encoding several phase-II detoxifying/antioxidant enzymes and related stress-responsive proteins, oxidative stress is prevented from damaging cells. , These enzymes and proteins include NAD­(P)­H: quinone oxidoreductase 1 (NQO1), heme oxygenase-1 (HO-1), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) . In addition, diallyl trisulfide (DATS) protects against oxidative stress-induced DNA damage and apoptosis in C2C12 cells, in part through the activation of Nrf2-mediated thioredoxin reductase 1 (TrxR1) induction via the ERK signaling pathway …”

“…27 In addition, diallyl trisulfide (DATS) protects against oxidative stressinduced DNA damage and apoptosis in C2C12 cells, in part through the activation of Nrf2-mediated thioredoxin reductase 1 (TrxR1) induction via the ERK signaling pathway. 28 In summary, thioether spice compounds possess certain antioxidant effects. The mechanism of antioxidative action of thioether spice compounds may involve the enhancement of antioxidant enzyme activities and the regulation of the Nrf2-ARE pathway.…”