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

• Published in: International journal of molecular sciences Vol. 24; no. 7; p. 6159
• Main Authors: Sharma, Sudha, Sharma, Papori, Subedi, Utsab, Bhattarai, Susmita, Miller, Chloe, Manikandan, Shrivats, Batinic-Haberle, Ines, Spasojevic, Ivan, Sun, Hong, Panchatcharam, Manikandan, Miriyala, Sumitra
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 24-03-2023; MDPI
• Subjects: 4-Hydroxynonenal; Apoptosis; Autophagy; Bioenergetics; Bmx protein; Cancer; Cardiolipin; Cardiomyocytes; Cell viability; Enzymes; Hypoxia; Injury prevention; Ischemia; L-Lactate dehydrogenase; Lactate dehydrogenase; Lipid peroxidation; Lipids; Mitochondria; Myocardial ischemia; Oxidation; Oxidative stress; Oxygen consumption; Peroxidation; Porphyrins; Pretreatment; Production increases; Proteins; Reperfusion; SOD2; superoxide; Superoxide dismutase
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms24076159

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.