The neoflavonoid latifolin isolated from Dalbergia odorifera attenuates hypoxia-reoxygenation injury by reactive oxygen species scavenging and Nrf2 activation in H9c2 cardiomyocyte

Metformin is a first-line drug for the management of type 2 diabetes. Recent studies suggested cardioprotective effects of metformin against ischemia/reperfusion injury. However, it remains elusive whether metformin provides direct protection against hypoxia/reoxygenation (H/R) injury in cardiomyocytes under normal or hyperglycemic conditions. This study in H9C2 rat cardiomyoblasts was designed to determine cell viability under H/R and high-glucose (HG, 33 mM) conditions and the effects of cotreatment with various concentrations of metformin (0, 1, 5, and 10 mM). We further elucidated molecular mechanisms underlying metformin-induced cytoprotection, especially the possible involvement of AMP-activated protein kinase (AMPK) and Jun NH(2)-terminal kinase (JNK). Results indicated that 5 mM metformin improved cell viability, mitochondrial integrity, and respiratory chain activity under HG and/or H/R (P<0.05). The beneficial effects were associated with reduced levels of reactive oxygen species generation and proinflammatory cytokines (TNF-α, IL-1α, and IL-6) (P<0.05). Metformin enhanced phosphorylation level of AMPK and suppressed HG + H/R induced JNK activation. Inhibitor of AMPK (compound C) or activator of JNK (anisomycin) abolished the cytoprotective effects of metformin. In conclusion, our study demonstrated for the first time that metformin possessed direct cytoprotective effects against HG and H/R injury in cardiac cells via signaling mechanisms involving activation of AMPK and concomitant inhibition of JNK.

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Bcl-2 prevents hypoxia/reoxygenation-induced cell death through suppressed generation of reactive oxygen species and upregulation of Bcl-2 proteins

Journal of Cellular Biochemistry ◽

10.1002/jcb.10723 ◽

2003 ◽

Vol 90 (5) ◽

pp. 914-924 ◽

Cited By ~ 13

Author(s):

Yasukazu Saitoh ◽

Rika Ouchida ◽

Nobuhiko Miwa

Keyword(s):

Reactive Oxygen Species ◽

Cell Death ◽

Reactive Oxygen ◽

Oxygen Species ◽

Hypoxia Reoxygenation

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Injury to Cultured Liver Endothelial Cells After Cold Preservation: Mediation by Reactive Oxygen Species that are Released Independently of the Known Trigger Hypoxia/Reoxygenation

Free Radical Biology and Medicine ◽

10.1016/s0891-5849(96)00618-1 ◽

1997 ◽

Vol 23 (3) ◽

pp. 392-400 ◽

Cited By ~ 22

Author(s):

Ursula Rauen ◽

Birgit Elling ◽

Herbert De Groot

Keyword(s):

Reactive Oxygen Species ◽

Endothelial Cells ◽

Reactive Oxygen ◽

Oxygen Species ◽

Cold Preservation ◽

Liver Endothelial Cells ◽

Hypoxia Reoxygenation

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Hesperidin Extracted from Citrus reticulata Blanco Protects Cardiac Mitochondria Against Hypoxia/Reoxygenation Injury

VNU Journal of Science Natural Sciences and Technology ◽

10.25073/2588-1140/vnunst.5328 ◽

2021 ◽

Vol 37 (4) ◽

Author(s):

Vu Thi Thu ◽

Phuong Thien Thuong

Keyword(s):

Reactive Oxygen Species ◽

Reactive Oxygen ◽

Cell Group ◽

Control Group ◽

Citrus Reticulata ◽

Oxygen Species ◽

Cardiac Mitochondria ◽

Citrus Reticulata Blanco ◽

H9c2 Cardiomyocytes ◽

Hypoxia Reoxygenation

This study was conducted to evaluate the protective effect of Hesperdin (Hes) extracted from Citrus reticulata Blanco on cardiac mitochondria in hypoxia/reoxygenation (HR) injury in vitro. Methods: H9C2 cardiomyocytes were cultured under normal (control), HR, and treatment conditions. The reactive oxygen species and calcium levels in experimental groups were analyzed by using suitable fluorescence kits. Results: The obtained results showed that the addition of Hes at dose of 0,01562 mg/mL sharply decreased the mitochondrial oxidative stress of H9C2 cells under HR conditions. In particular, Hes showed the remarkable efficiency in maintaing cellular calcium levels. In HR-exposed H9C2 cell group, the hydrogen peroxide and superoxide levels were highly increased compared to those in control group (1,54±0,06 and 1,74±0,38, p<0,05). HR also strongly induced the elevation of cytosolic Ca²⁺ and mitochondial Ca²⁺ of H9C2 cardiomyocytes with the values were 1,96±0,05% and 1,62±0,33 (ratio to control, p<0,05), respectively. Interestingly, post-hypoxic supplementation of Hes effectivelly abolished the negative incresement of these indicators with the lower levels of reactive oxygen species and the better modulation of Ca²⁺ homeostasis. Conclusion: The present results are pilot data on the effects of Hes in protecting cardiac mitochondria against HR injury.

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