Hydrogen sulfide attenuates doxorubicin-induced cardiotoxicity by inhibiting the expression of peroxiredoxin III in H9c2 cells

Abstract

Doxorubicin (DOX) is a widely used chemotherapeutic agent, which can give rise to severe cardiotoxicity, limiting its clinical use. Preliminary evidence suggests that hydrogen sulfide (H2S) may exert protective effects on DOX‑induced cardiotoxicity. Therefore, the aim of the present study was to investigate whether peroxiredoxin III is involved in the cardioprotection of H2S against DOX‑induced cardiotoxicity. The results demonstrated that DOX not only markedly induced injuries, including cytotoxicity and apoptosis, it also increased the expression levels of peroxiredoxin III. Notably, pretreatment with sodium hydrosulfide significantly attenuated the DOX‑induced decrease in cell viability and increase in apoptosis, and also reversed the increased expression levels of peroxiredoxin III in H9c2 cardiomyocytes. In addition, pretreatment of the H9c2 cells with N‑acetyl‑L‑cysteine, a scavenger of reactive oxygen species, prior to exposure to DOX markedly decreased the expression levels of peroxiredoxin III. In conclusion, the results of the present study suggested that exogenous H2S attenuates DOX‑induced cardiotoxicity by inhibiting the expression of peroxiredoxin III in H9c2 cells. In the present study, the apoptosis of H9c2 cardiomyocytes was assessed using an methyl thiazolyl tetrazolium assay and Hoechst staining. The levels of Prx III and cystathionine-γ-lyase were examined by western blotting.

Zofenopril Protects Against Myocardial Ischemia–Reperfusion Injury by Increasing Nitric Oxide and Hydrogen Sulfide Bioavailability

“…Recently, exogenously delivered H 2 S and/or enhancement of the endogenous H 2 S signaling pathway has been shown to limit cardiac injury acutely after I/R injury . Indeed, it has been demonstrated that H 2 S has effects on INF sparing after I/R injury but is also able to exert potent antioxidant, antiapoptotic, anti‐inflammatory, and proangiogenic effects under various stressors. In addition, the biological profile of H 2 S is similar to that of NO, and these 2 endogenous gaseous signaling molecules may affect one another with respect to their production and cell signaling molecular pathways.…”

Protective Mechanism of Hydrogen Sulfide against Chemotherapy-Induced Cardiotoxicity

“…Moreover, they observed that selectively inhibiting ERK1/2 could further obtain the above-mentioned effects of H 2 S. Liu and his colleagues also found that doxorubicin could induce cytotoxicity through increasing the peroxiredoxin III expression. They pretreated H9c2 cells with NaHS and found that the cell viability was increased, cell apoptosis attenuated, and the peroxiredoxin III overexpression reversed (Liu et al, 2016a ). Therefore, H 2 S might play an antioxidant role in doxorubicin-induced cardiotoxicity via inhibiting ROS generation, ER stress-related proteins levels, peroxiredoxin III expression, and ERK1/2 phosphorylation and activating Nrf2 and its downstream pathway.…”

“…Once produced, H 2 S is broken down rapidly and participates in many pathophysiological processes (Tang et al, 2006 ; Du et al, 2011 , 2014 ; Sun et al, 2011 ; Altaany et al, 2014 ; Yang and Wang, 2015 ; Bian et al, 2016 ; Cao and Bian, 2016 ; Panthi et al, 2016 ). More importantly, recent evidence shows that H 2 S may play cytoprotective role in heart diseases (Shen et al, 2015 ; Liu et al, 2016a ; Szabo, 2016 ; Huang et al, 2017 ). Here, we mainly reviewed the cardioprotective role of H 2 S in chemotherapy and its possible mechanisms.…”

H2S improves doxorubicin-induced myocardial fibrosis by inhibiting oxidative stress and apoptosis via Keap1-Nrf2

“…One of our previous studies also found that H S also improved diabetic myocardial fibrosis, which is associated with the inhibition of oxidative stress [ 31 ]. In an experiment in vitro , H S was also found to improve the cardiotoxicity of doxorubicin, and H S sustained release agent Diallyl trisulfide inhibited doxorubicin-induced myocardial apoptosis [ 13 , 14 ]. The results of this experiment revealed that after the intervention with H S donor NaHS, the cardiac function of the rats in the DOX+H S group was improved, EF and FS were increased, LVEDD and LVESD were significantly decreased, and HW/BW was significantly decreased, compared with DOX group.…”

“…The role of gaseous signal molecule H S in doxorubicin-induced myocardial fibrosis in rats and its internal mechanism has been rarely studied. Some studies have revealed that H S can relieve doxorubicin-induced myocardial damage, thereby improving the cardiac function of doxorubicin-induced myocardial fibrosis in rats [ 13 , 14 ]. Thus, we assume that H S may improve doxorubicin-induced myocardial fibrosis in rats, and the relevant mechanism may be correlated with the inhibition of oxidative stress, inflammatory response, and apoptosis by regulating the Keap1-Nrf2 signaling pathway.…”