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Mn(III) Porphyrin, MnTnBuOE-2-PyP5+, Commonly Known as a Mimic of Superoxide Dismutase Enzyme, Protects Cardiomyocytes from Hypoxia/Reoxygenation Induced Injury via Reducing Oxidative Stress.

Abstract
Myocardial ischemia-reperfusion injury (I/R) causes damage to cardiomyocytes through oxidative stress and apoptosis. We investigated the cardioprotective effects of MnTnBuOE-2-PyP5+ (BMX-001), a superoxide dismutase mimic, in an in vitro model of I/R injury in H9c2 cardiomyocytes. We found that BMX-001 protected against hypoxia/reoxygenation (H/R)-induced oxidative stress, as evident by a significant reduction in intracellular and mitochondrial superoxide levels. BMX-001 pre-treatment also reduced H/R-induced cardiomyocyte apoptosis, as marked by a reduction in TUNEL-positive cells. We further demonstrated that BMX-001 pre-treatment significantly improved mitochondrial function, particularly O2 consumption, in mouse adult cardiomyocytes subjected to H/R. BMX-001 treatment also attenuated cardiolipin peroxidation, 4-hydroxynonenal (4-HNE) level, and 4-HNE adducted proteins following H/R injury. Finally, the pre-treatment with BMX-001 improved cell viability and lactate dehydrogenase (LDH) activity in H9c2 cells following H/R injury. Our findings suggest that BMX-001 has therapeutic potential as a cardioprotective agent against oxidative stress-induced H/R damage in H9c2 cardiomyocytes.
AuthorsSudha Sharma, Papori Sharma, Utsab Subedi, Susmita Bhattarai, Chloe Miller, Shrivats Manikandan, Ines Batinic-Haberle, Ivan Spasojevic, Hong Sun, Manikandan Panchatcharam, Sumitra Miriyala
JournalInternational journal of molecular sciences (Int J Mol Sci) Vol. 24 Issue 7 (Mar 24 2023) ISSN: 1422-0067 [Electronic] Switzerland
PMID37047131 (Publication Type: Journal Article)
Chemical References
  • Mn(III) meso-tetrakis(N-n-butoxyethylpyridinium-2-yl)porphyrin
  • Porphyrins
  • Antioxidants
  • Superoxide Dismutase
Topics
  • Mice
  • Animals
  • Myocytes, Cardiac (metabolism)
  • Porphyrins (pharmacology)
  • Hypoxia (drug therapy, metabolism)
  • Oxidative Stress
  • Antioxidants (pharmacology)
  • Cell Hypoxia
  • Superoxide Dismutase (metabolism)
  • Apoptosis

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