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.
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Authors | Sudha Sharma, Papori Sharma, Utsab Subedi, Susmita Bhattarai, Chloe Miller, Shrivats Manikandan, Ines Batinic-Haberle, Ivan Spasojevic, Hong Sun, Manikandan Panchatcharam, Sumitra Miriyala |
Journal | International journal of molecular sciences
(Int J Mol Sci)
Vol. 24
Issue 7
(Mar 24 2023)
ISSN: 1422-0067 [Electronic] Switzerland |
PMID | 37047131
(Publication Type: Journal Article)
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Chemical References |
- Mn(III) meso-tetrakis(N-n-butoxyethylpyridinium-2-yl)porphyrin
- Porphyrins
- Antioxidants
- Superoxide Dismutase
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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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