The effects of a high dose of ascorbate on ischemia-reperfusion-induced mitochondrial dysfunction in canine hearts

Nishinaka, Yasuto; Sugiyama, Satoru; Yokota, Mitsuhiro; Saito, Hidehiko; Ozawa, Takayuki

doi:10.1007/bf01745863

Cited by 26 publications

(15 citation statements)

References 23 publications

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“…2 Instead, electron flow through the ETC upon reperfusion was described as a source of potentially detrimental reactive oxygen species (ROS), proposed to trigger ischaemia-reperfusion (I/R) injuries. 2 Conversely, the therapeutic use of untargeted antioxidants such as vitamin C for post-ischaemic cardioprotection has given contradictory results, [4][5][6][7][8][9] and itself produced detrimental side effects when therapeutically used. 10 These seemingly contradictory results were thought to be due to biphasic effects of ROS with high ROS concentrations leading to damage and lower concentrations eliciting adaptive responses.…”

Section: Introductionmentioning

confidence: 99%

Respiratory chain signalling is essential for adaptive remodelling following cardiac ischaemia

Szibor

Schreckenberg

Gizatullina

et al. 2020

J Cellular Molecular Medi

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Cardiac ischaemia‐reperfusion (I/R) injury has been attributed to stress signals arising from an impaired mitochondrial electron transport chain (ETC), which include redox imbalance, metabolic stalling and excessive production of reactive oxygen species (ROS). The alternative oxidase (AOX) is a respiratory enzyme, absent in mammals, that accepts electrons from a reduced quinone pool to reduce oxygen to water, thereby restoring electron flux when impaired and, in the process, blunting ROS production. Hence, AOX represents a natural rescue mechanism from respiratory stress. This study aimed to determine how respiratory restoration through xenotopically expressed AOX affects the re‐perfused post‐ischaemic mouse heart. As expected, AOX supports ETC function and attenuates the ROS load in post‐anoxic heart mitochondria. However, post‐ischaemic cardiac remodelling over 3 and 9 weeks was not improved. AOX blunted transcript levels of factors known to be up‐regulated upon I/R such as the atrial natriuretic peptide (Anp) whilst expression of pro‐fibrotic and pro‐apoptotic transcripts were increased. Ex vivo analysis revealed contractile failure at nine but not 3 weeks after ischaemia whilst label‐free quantitative proteomics identified an increase in proteins promoting adverse extracellular matrix remodelling. Together, this indicates an essential role for ETC‐derived signals during cardiac adaptive remodelling and identified ROS as a possible effector.

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Section: Introductionmentioning

confidence: 99%

Respiratory chain signalling is essential for adaptive remodelling following cardiac ischaemia

Szibor

Schreckenberg

Gizatullina

et al. 2020

J Cellular Molecular Medi

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“…Ascorbate is known to have a multiplicity of antioxidant properties, including the ability to act as a reducing agent to scavenge free radicals directly, and sparing other antioxidants, such as ␣-tocopherol (vitamin E) and GSH (35,42). Furthermore, a previous study has shown that administration of high-dose ascorbate attenuates myocardial I/R injury and mitochondrial dysfunction, suggesting an antioxidant action localized at or near the mitochondrial compartment (40). Based on studies demonstrating similar antioxidant actions and a mutual sparing effect between GSH and ascorbate (37,57), there appears to be some functional redundancy between these two antioxidant systems.…”

Section: Discussionmentioning

confidence: 99%

Glutathione peroxidase deficiency exacerbates ischemia-reperfusion injury in male but not female myocardium: insights into antioxidant compensatory mechanisms

Lim

Bryan

Jain

et al. 2009

American Journal of Physiology-Heart and Circulatory Physiology

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The female sex has been associated with increased resistance to acute myocardial ischemia-reperfusion (I/R) injury. While enhanced antioxidant capacity has been implicated in female cardioprotection, there is little evidence to support this assumption. Previous studies have shown an important role of cellular glutathione peroxidase (GPx1) in protection of the myocardium from I/R injury. Whether GPx1 is mechanistic in the protection of female myocardium, post-I/R, has not been examined. We utilized a murine model with homozygous deletion of GPx1 and examined its impact on postischemic myocardial recovery in male and female mice. Following I/R, male GPx1(-/-) hearts were more susceptible to contractile and diastolic dysfunction, and this was associated with increased protein carbonyls, a marker of oxidative stress. In contrast, GPx1 deficiency in female hearts did not exacerbate dysfunction or oxidative stress post-I/R. Both wild-type and GPx1(-/-) female hearts exhibited reduced creatine kinase leakage and a more favorable ascorbate redox status compared with males. Following I/R, female GPx1(-/-) hearts showed a comparable decrease in glutathione redox status as their male counterparts; however, they exhibited a greater decrease in nitrate-to-nitrite ratio, suggesting a higher consumption of nitrate in female GPx1(-/-) hearts. Our findings demonstrate that GPx1 is critical for cardioprotection during I/R in male, but not female, mice. The maintenance of cardioprotection in female mice lacking GPx1 post-I/R may be due to an improved ascorbate redox homeostasis and enhanced nitrate-to-nitrite conversion, which would predictably be accompanied by enhanced production of cardioprotective nitric oxide.

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“…There have been reports showing a close correlation between the production of ROS and simultaneous consumption of endogenous antioxidants 151,152 . Indirect evidence consistent with this view is the cardioprotective effects of free radical scavengers and antioxidant supplements 161,162,163 . New research finds that rats given oral low dose of quercetin significantly protected against the injury that normally occurs during ischemia and reperfusion 164 .…”

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confidence: 82%

Role of quercetin in cardiovascular diseases

Lakhanpal¹,

Kumar²

2008

Internet Journal of Medical Update - EJOURNAL

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Cardiovascular disease constitutes a major public health concern in industrialized nations. Over recent decades, a large body of evidence has accumulated indicating that oxidative stress induced free radicals play a critical role in cellular processes implicated in atherosclerosis and many other heart diseases. However a diet high in antioxidants is associated with a reduced risk of cardiovascular disease. The compound quercetin is a dietary antioxidant with a polyphenolic structure that is present in many foods, such as onion, apples, wine and tea. An increased intake of quercetin has been correlated with a decrease in the risk of cardiovascular diseases. Quercetin has been reported to exhibit a wide range of biological and pharmacological effects in animals and man besides its antioxidative and free radical scavenging actions. This paper reviews various steps of oxidative stress mediated atherogenesis and their signaling pathways and also emphasizes the role of quercetin in controlling oxidative stress and reducing the incidence of cardiovascular diseases.

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The effects of a high dose of ascorbate on ischemia-reperfusion-induced mitochondrial dysfunction in canine hearts

Cited by 26 publications

References 23 publications

Respiratory chain signalling is essential for adaptive remodelling following cardiac ischaemia

Respiratory chain signalling is essential for adaptive remodelling following cardiac ischaemia

Glutathione peroxidase deficiency exacerbates ischemia-reperfusion injury in male but not female myocardium: insights into antioxidant compensatory mechanisms

Role of quercetin in cardiovascular diseases

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