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Attenuation of cardiac ischemia-reperfusion injury by sodium thiosulfate is partially dependent on the effect of cystathione beta synthase in the myocardium

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Abstract

Our early studies have shown that sodium thiosulfate (STS) treatment attenuated the ischemia-reperfusion (IR)-induced injury in an isolated rat heart model by decreasing apoptosis, oxidative stress, and preserving mitochondrial function. Hydrogen sulfide, the precursor molecule is reported to have similar efficacy. This study aims to investigate the role of endogenous hydrogen sulfide in STS-mediated cardioprotection against IR in an isolated rat heart model. d, l-propargylglycine (PAG), an inhibitor of cystathionine γ-lyase was used as endogenous H2S blocker. In addition, we used the hypoxia-reoxygenation (HR) model to study the impact of STS in cardiomyocytes (H9C2) and fibroblast (3T3) cells. STS treatment to animal and cells prior to IR or HR decreased cell injury. The sensitivity of H9C2 and 3T3 cells towards HR (6 h hypoxia followed by 12 h reoxygenation) challenge varies, where, 3T3 cells exhibited higher cell death (54%). Cells treated with PAG prior to STS abrogate the protective effect in 3T3 (cell viability 61%) but not in H9C2 (cell viability 82%). Further evaluation in rat heart model showed partial recovery (46% RPP) of heart from those hearts pretreated with PAG prior to STS condition. In conclusion, we demonstrated that STS-mediated cardioprotection to IR-challenged rat heart is not fully dependent on endogenous H2S level and this dependency may be linked to higher fibroblast content in rat heart.

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Acknowledgements

The authors would like to acknowledge the Indian Council for Medical Research (ICMR), Government of India, New Delhi, for supporting this research through grant-in-aid (No. 5/4/1-14/12-NCD-II).

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Authors and Affiliations

  1. School of Chemical and Biotechnology, SASTRA Deemed University, Thanjavur, India

    Srijanani Kannan, Sri Rahavi Boovarahan, Jeyashri Rengaraju, Priyanka Prem & Gino A. Kurian

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  1. Srijanani Kannan
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  2. Sri Rahavi Boovarahan
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Correspondence to Gino A. Kurian.

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The study protocol involving experimentation on animals was approved by the Committee for the Purpose of Control and Supervision of Experiments on Animals (CPCSEA), India, with prior approval of the Institutional Animal Ethical Committee (IAEC, SASTRA University, No.: 229/SASTRA/IAEC/RPP).

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Kannan, S., Boovarahan, S.R., Rengaraju, J. et al. Attenuation of cardiac ischemia-reperfusion injury by sodium thiosulfate is partially dependent on the effect of cystathione beta synthase in the myocardium. Cell Biochem Biophys 77, 261–272 (2019). https://doi.org/10.1007/s12013-019-00871-8

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