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KMID : 0043320210440060605
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Archives of Pharmacal Research
2021 Volume.44 No. 6 p.605 ~ p.620
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Inhibition of PI3K/mTOR/KATP channel blunts sodium thiosulphate preconditioning mediated cardioprotection against ischemia?reperfusion injury
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Boovarahan Sri Rahavi
Venkatasubramanian Harini
Sharma Nidhi
Venkatesh Sushma
Prem Priyanka
Kurian Gino A.
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Abstract
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Recent studies have shown that pre and postconditioning the heart with sodium thiosulfate (STS) attenuate ischemia?reperfusion (IR) injury. However, the underlying mechanism involved in the cardioprotective signaling pathway is not fully explored. This study examined the existing link of STS mediated protection (as pre and post-conditioning agents) with PI3K, mTOR, and mPTP signaling pathways using its respective inhibitors. STS was administered to the isolated perfused rat heart through Kreb’s Heinselit buffer before ischemia (precondition: SIPC) and reperfusion (postcondition: SPOC) in the presence and absence of the PI3K, mTOR, and mPTP signaling pathway inhibitors (wortmannin, rapamycin, and glibenclamide respectively). SIPC failed to improve the IR injury-induced altered cardiac hemodynamics, increased infarct size, and the release of cardiac injury markers in the presence of these inhibitors. On the other hand, the SPOC protocol effectively rendered the cardioprotection even in the PI3K/mTOR/KATP inhibitors presence. Interestingly, the SIPC’s identified mode of action viz reduction in oxidative stress and the preservation of mitochondrial function were lost in the inhibitors’ presence. Based on the above results, we conclude that the underlying mechanism of SIPC mediated cardioprotection works via the PI3K/mTOR/KATP signaling pathway axis activation.
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KEYWORD
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Ischemia?reperfusion injury, Sodium thiosulphate Precondition, Sodium thiosulphate Postcondition, Wortmannin, Rapamycin, Glibenclamide
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