Potent mitochondria-targeted peptides reduce myocardial infarction in rats

Cho, Janghyun; Won, Kyung-Heon; Wu, Dunli; Soong, Yi; Liu, Shaoyi; Szeto, Hazel H.; Hong, Mun K.

doi:10.1097/01.mca.0000236285.71683.b6

Cited by 130 publications

(101 citation statements)

References 19 publications

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“…SarcKATP channels opening reduces the action potential duration and effective refractory period (Aidonidis et al, 2009;Ferrier & Howlett, 2005) which in turn increases the incidence of cardiac arrhythmia (Billman, 2008;Billman et al, 2004). There is credible evidence that during reperfusion, production of oxygen free radicals increase in ischemic tissue (Bolli et al, 1989;Manning et al, 1988) and the use of ROS (reactive oxygen species) scavengers is associated with successful decrease in the reperfusion-induced arrhythmias (Cho et al, 2007;Hicks et al, 2007;Konya et al, 1992). Existing documents show the antioxidant properties of saffron (Asdaq & Inamdar, 2010;Hosseinzadeh et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

Protective effects of saffron (Crocus sativus) against lethal ventricular arrhythmias induced by heart reperfusion in rat: A potential anti-arrhythmic agent

Joukar

Ghasemipour-Afshar

Sheibani

et al. 2013

Pharmaceutical Biology

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Context: Saffron (Crocus sativus L.) has been used as a cuisine spice in eastern and western societies for thousands of years. In traditional medicine, saffron is recommended for the treatment of various kinds of disorders including heart palpitations. Objective: We investigated the hypothesis of the protective effect of saffron on lethal cardiac arrhythmias induced by heart ischemia-reperfusion in rat. Materials and methods: Animals were divided into a control (CTL) group that received tap water, Saf50, Saf100 and Saf200 groups that were orally treated with aqueous extracts of saffron, at dosages of 50, 100 and 200 mg/kg/day, respectively, and amiodarone (Amio) group that orally received 30 mg/kg/day for seven days. On day 8, heart ischemia-reperfusion was induced by ligation and releasing of the left anterior descending coronary artery. Results: During reperfusion, the numbers and durations of ventricular fibrillation (VF) decreased in all groups compared to the CTL group (p50.05). Ventricular tachycardia (VT)/VF numbers (3.2 AE 1.2), durations (4.9 AE 2.6) and also arrhythmia severity (1.9 AE 0.35) were decreased significantly in the Saf100 group versus CTL group values (18.4 AE 11.6, 52 AE 31 and 3.3 AE 0.3, respectively). The PR and QTcn intervals of ECG were significantly longer in the Saf200 group (p50.001 versus CTL). The other doses of saffron only significantly prolonged the QTcn interval. Conclusion:The results suggest that pretreatment with saffron, especially at the dosage of 100 mg/kg/day, attenuates the susceptibility and incidence of fatal ventricular arrhythmia during the reperfusion period in the rat. This protective effect is apparently mediated through reduction of electrical conductivity and prolonging the action potential duration.

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Section: Discussionmentioning

confidence: 99%

Protective effects of saffron (Crocus sativus) against lethal ventricular arrhythmias induced by heart reperfusion in rat: A potential anti-arrhythmic agent

Joukar

Ghasemipour-Afshar

Sheibani

et al. 2013

Pharmaceutical Biology

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“…This small peptide with dual function has been reported to significantly increase cardiac ATP content, decrease oxidative stress, and reduce myocardial infarct size in rats. 22,23 In this study, we examined the therapeutic potential of SS-31 to prevent AKI in rats caused by warm IR injury. …”

mentioning

confidence: 99%

Mitochondria-Targeted Peptide Accelerates ATP Recovery and Reduces Ischemic Kidney Injury

Szeto

Liu

Soong

et al. 2011

Journal of the American Society of Nephrology

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267

244

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The burst of reactive oxygen species (ROS) during reperfusion of ischemic tissues can trigger the opening of the mitochondrial permeability transition (MPT) pore, resulting in mitochondrial depolarization, decreased ATP synthesis, and increased ROS production. Rapid recovery of ATP upon reperfusion is essential for survival of tubular cells, and inhibition of oxidative damage can limit inflammation. SS-31 is a mitochondria-targeted tetrapeptide that can scavenge mitochondrial ROS and inhibit MPT, suggesting that it may protect against ischemic renal injury. Here, in a rat model of ischemia-reperfusion (IR) injury, treatment with SS-31 protected mitochondrial structure and respiration during early reperfusion, accelerated recovery of ATP, reduced apoptosis and necrosis of tubular cells, and abrogated tubular dysfunction. In addition, SS-31 reduced medullary vascular congestion, decreased IR-mediated oxidative stress and the inflammatory response, and accelerated the proliferation of surviving tubular cells as early as 1 day after reperfusion. In summary, these results support MPT as an upstream target for pharmacologic intervention in IR injury and support early protection of mitochondrial function as a therapeutic maneuver to prevent tubular apoptosis and necrosis, reduce oxidative stress, and reduce inflammation. SS-31 holds promise for the prevention and treatment of acute kidney injury. Acute kidney injury (AKI) develops in 5% of hospitalized patients and is associated with significant morbidity. Ischemia is the most common cause of AKI. Despite our current knowledge of the pathophysiology underlying renal ischemia-reperfusion (IR) injury, pharmacologic interventions have not reduced the mortality and morbidity associated with AKI.Rapid recovery of ATP after ischemia is essential for cell survival after IR injury. A profound reduction in intracellular ATP occurs early after onset of ischemia and leads to cytoskeletal derangements, membrane alterations, and cell death by apoptosis and necrosis. 1 Disruption of the cytoskeleton leads to redistribution of integrins and Na ϩ ,K ϩ -ATPase from the basal membrane, resulting in detachment of viable cells from the basement membrane and impairment of Na ϩ reabsorption. The mode of cell death depends on the duration of ischemia and the region of the nephron. Cell death is usually restricted to the outer medullary region where oxygen tension drops precipitously at the corticomedullary junction. 2 The proximal tubules are particularly susceptible to IR injury because they have minimal glycolytic capacity and must rely on mitochondrial metabolism for ATP synthesis. [3][4][5] Ischemia causes damage to all components of the mitochondrial electron transport chain (ETC), resulting in decreased oxidative phosphorylation upon reperfusion. 6 In addition, mitochondria are the primary source of reactive oxygen species (ROS). 6,7 Mitochondria can undergo further damage upon reperfusion because of mitochondrial permeability transition (MPT). During ischemia, elevated mitocho...

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“…Using these peptides in an animal model of ischaemia/reperfusion injury improves cardiac function [112]. Whereas treatment with SS peptides attenuated mitochondrial H2O2 release induced by a high-fat diet and preserved insulin sensitivity in skeletal muscle [113]. Importantly, pre-clinical studies support the use of these peptides during ischaemia/reperfusion injury and neurodegenerative disorders [114].…”

Section: Protection Against Oxidative Stress and "Igf-i Deficiency Comentioning

confidence: 92%

Protection Against Oxidative Stress and “IGF-I Deficiency Conditions”

Morón¹,

Castilla‐Cortázar²

2012

Antioxidant Enzyme

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Potent mitochondria-targeted peptides reduce myocardial infarction in rats

Cited by 130 publications

References 19 publications

Protective effects of saffron (Crocus sativus) against lethal ventricular arrhythmias induced by heart reperfusion in rat: A potential anti-arrhythmic agent

Protective effects of saffron (Crocus sativus) against lethal ventricular arrhythmias induced by heart reperfusion in rat: A potential anti-arrhythmic agent

Mitochondria-Targeted Peptide Accelerates ATP Recovery and Reduces Ischemic Kidney Injury

Protection Against Oxidative Stress and “IGF-I Deficiency Conditions”

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