Dimethyl Sulfoxide Attenuates Hydrogen Peroxide‐Induced Injury in Cardiomyocytes via Heme Oxygenase‐1

Abstract

The antioxidant property of dimethyl sulfoxide (DMSO) was formerly attributed to its direct effects. Our former study showed that DMSO is able to induce heme oxygenase-1 (HO-1) expression in endothelial cells, which is a potent antioxidant enzyme. In this study, we hypothesized that the antioxidant effects of DMSO in cardiomyocytes are mediated or partially mediated by increased HO-1 expression. Therefore, we investigated whether DMSO exerts protective effects against H2 O2 -induced oxidative damage in cardiomyocytes, and whether HO-1 is involved in DMSO-imparted protective effects, and we also explore the underlying mechanism of DMSO-induced HO-1 expression. Our study demonstrated that DMSO pretreatment showed a cytoprotective effect against H2 O2 -induced oxidative damage (impaired cell viability, increased apopototic cells rate and caspase-3 level, and increased release of LDH and CK) and this process is partially mediated by HO-1 upregulation. Furthermore, our data showed that the activation of p38 MAPK and Nrf2 translocation are involved in the HO-1 upregulation induced by DMSO. This study reports for the first time that the cytoprotective effect of DMSO in cardiomyocytes is partially mediated by HO-1, which may further explain the mechanisms by which DMSO exerts cardioprotection on H2 O2 injury. J. Cell. Biochem. 115: 1159-1165, 2014. © 2013 Wiley Periodicals, Inc.

Omeprazole induces heme oxygenase-1 in fetal human pulmonary microvascular endothelial cells via hydrogen peroxide-independent Nrf2 signaling pathway

“…The most plausible reasons for these discrepant results may be related to differences in species, cells and organs studied, concentration of OM used, and the nature and duration of the experimental injury. Consistent with other studies (Kruger et al , 2006; Man et al , 2014), H 2 O 2 independently increased HO-1 expression (Fig. 6), indicating that OM might activate Nrf2 via H 2 O 2 .…”

“…Additionally, investigators have shown that DMSO induces HO-1 expression via Nrf2 activation (Liang et al , 2011; Man et al , 2014); however, the concentration at which DMSO exerts these effects are significantly higher than that used in our study. So, it is highly unlikely that DMSO independently increased HO-1 expression in our study.…”

P2X7 receptor antagonism ameliorates renal dysfunction in a rat model of sepsis

“…DMSO exerts anti‐inflammatory effects as a hydroxyl radical scavenger (Man et al. ). DMSO also decreases IL‐1 β mRNA transcription and reduces inflammation (Ahn et al.…”

MMI-0100 inhibits cardiac fibrosis in myocardial infarction by direct actions on cardiomyocytes and fibroblasts via MK2 inhibition

“…The consequences of maintaining dysfunctional mitochondria is a bioenergetics catastrophe, culminating in the disruption of the plasma membrane, resulting in necrosis [60, 61], which may explain the divergent apoptosis and necrosis results MMI-0100 affords cardiomyocytes in the present study. The unexpected early LDH release and necrosis occurring before caspase-3/7 activation may have to do with the use of DMSO as vehicle, which has been reported to attenuate oxidative stress induced apoptosis via inhibiting p38 to exert a cardioprotective effects via regulation of heme oxygenase-1 [62, 63]. …”