Selective retroinfusion of GSH and cariporide attenuates myocardial ischemia–reperfusion injury in a preclinical pig model

Kupatt, Christian; Hinkel, Rabea; Horstkotte, Jan; Deiss, M.; Brühl, Marie-Luise von; Bilzer, Manfred; Boekstegers, Peter

doi:10.1016/j.cardiores.2003.11.012

Cited by 31 publications

(15 citation statements)

References 43 publications

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“…Oxidative stress related to heart was evident in patients undergoing by-pass surgery, where oxidized glutathione (GSSG) accumulation was found to be negatively correlated with the functional recovery of the myocardium [ 6 ]. Currently, the ratio of oxidized glutathione (GSSG) to reduced glutathione (GSH) is used as a marker of oxidative stress, considering the fact that GSH, a tripeptide ( γ -glutamylcysteinylglycine) containing free thiol group, is one of the most important scavengers of ROS in the heart [ 7 , 8 ]. Furthermore, it can act as an antioxidant in association with glutathione peroxidase (GPx) catalyzed reaction by providing reducing equivalents and thereby helping in the reduction of lipid hydro peroxides ( Figure 1 ).…”

Section: Oxidative Stress In Cardiovascular Diseasesmentioning

confidence: 99%

The Role of Oxidative Stress in Myocardial Ischemia and Reperfusion Injury and Remodeling: Revisited

Kurian

Rajagopal

Vedantham

et al. 2016

Oxidative Medicine and Cellular Longevity

259

175

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Oxidative and reductive stress are dual dynamic phases experienced by the cells undergoing adaptation towards endogenous or exogenous noxious stimulus. The former arises due to the imbalance between the reactive oxygen species production and antioxidant defenses, while the latter is due to the aberrant increase in the reducing equivalents. Mitochondrial malfunction is the common denominator arising from the aberrant functioning of the rheostat that maintains the homeostasis between oxidative and reductive stress. Recent experimental evidences suggest that the maladaptation during oxidative stress could play a pivotal role in the pathophysiology of major cardiovascular diseases such as myocardial infraction, atherosclerosis, and diabetic cardiovascular complications. In this review we have discussed the role of oxidative and reductive stress pathways in the pathogenesis of myocardial ischemia/reperfusion injury and diabetic cardiomyopathy (DCM). Furthermore, we have provided impetus for the development of subcellular organelle targeted antioxidant drug therapy for thwarting the deterioration of the failing myocardium in the aforementioned cardiovascular conditions.

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Section: Oxidative Stress In Cardiovascular Diseasesmentioning

confidence: 99%

The Role of Oxidative Stress in Myocardial Ischemia and Reperfusion Injury and Remodeling: Revisited

Kurian

Rajagopal

Vedantham

et al. 2016

Oxidative Medicine and Cellular Longevity

259

175

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“…Therefore, further investigation was performed with a focus on the antioxidant properties involved in the cardioprotective effects of YLSF. As an endogenous antioxidant enzyme, SOD plays an important role in protecting the cells from oxidative damage by converting O 2- into H 2 O 2 , and GSH is an important non-enzymatic antioxidant defense process required to maintain the normal redox state of cells and to counteract the deleterious effects of oxidative stress [28]. Our results showed that the significant decrease in the GSH-Px and SOD levels in the model group was enhanced by YLSF, which indicated the potential of YLSF to counteract oxidative damage and to reinforce antioxidant defenses.…”

Section: Discussionmentioning

confidence: 99%

Mechanism of the Protective Effect of Yulangsan Flavonoid on Myocardial Ischemia/Reperfusion Injury in Rats

Zhang

Liang

Lin

et al. 2014

Cell Physiol Biochem

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Aims: Effect and mechanism of Yulangsan flavonoid (YLSF) on rat myocardial ischemia/reperfusion injury (MI/RI) has been investigated. Methods: Sprague-Dawley (SD) rats were randomly divided into seven groups (sham group, model group and NS group: 2 mL of normal saline/kg body weight was administered; diltiazem group: 5 mg of diltiazem hydrochloride/kg body weight was administered; YLSFL, YLSFM and YLSFH groups: 20, 40 and 80 mg of YLSF/kg body weight was administered) and the MI/RI model was established. Myocardial infarct area, levels of myocardial enzymes and nitric oxide synthase (NOS) were measured. Caspase-3 and adenine nucleotide translocator-1 (ANT1) mRNA expression were evaluated by reverse transcription polymerase chain reaction (RT-PCR). Pathological structure and cardiocyte ultrastructure were also analysed. Results: Compared with the MI/RI group, pretreatment with YLSF or diltiazem hydrochloride decreased the infarct area, levels of inducible nitric oxide synthase (iNOS), caspase-3 as well as the leakage of myocardial enzyme and increased activities of total nitric oxide synthase (tNOS) as well as constitutive nitric oxide synthase (cNOS). Cellular edema and the infiltration of inflammatory cells were alleviated. Conclusions: The experiment showed that YLSF protected the heart against MI/RI, possibly by reducing lipid peroxidation damage, regulating NOS activity and modulating the apoptosis genes expression.

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“…Exogenous GSH supplementation in pigs significantly increases myocardial GSH content and resistance to ischemiareperfusion injury (36,49). Additionally, apoptosis and oxidative stress in isolated hearts perfused with high levels of glucose were attenuated by addition of GSH to the perfusion buffer (4).…”

Section: H773mentioning

confidence: 99%

Cardiomyocyte apoptosis induced by short-term diabetes requires mitochondrial GSH depletion

Ghosh¹,

Pulinilkunnil²,

Yuen³

et al. 2005

American Journal of Physiology-Heart and Circulatory Physiology

129

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Oxidative stress due to excessive reactive oxygen species (ROS) and depleted antioxidants such as glutathione (GSH) can give rise to apoptotic cell death in acutely diabetic hearts and lead to heart disease. At present, the source of these cardiac ROS or the subcellular site of cardiac GSH loss [i.e., cytosolic (cGSH) or mitochondrial (mGSH) GSH] has not been completely elucidated. With the use of rotenone (an inhibitor of the electron transport chain) to decrease the excessive ROS in acute streptozotocin (STZ)-induced diabetic rat heart, the mitochondrial origin of ROS was established. Furthermore, mitochondrial damage, as evidenced by loss of membrane potential, increases in oxidative stress, and reduction in mGSH was associated with increased apoptosis via increases in caspase-9 and -3 activities in acutely diabetic hearts. To validate the role of mGSH in regulating cardiac apoptosis, L-buthionine-sulfoximine (BSO; 10 mmol/kg ip), which blocks GSH synthesis, or diethyl maleate (DEM; 4 mmol/kg ip), which inactivates preformed GSH, was administered in diabetic rats for 4 days after STZ administration. Although both BSO and DEM lowered cGSH, they were ineffective in reducing mGSH or augmenting cardiomyocyte apoptosis. To circumvent the lack of mGSH depletion, BSO and DEM were coadministered in diabetic rats. In this setting, mGSH was undetectable and cardiac apoptosis was further aggravated compared with the untreated diabetic group. In a separate group, GSH supplementation induced a robust amplification of mGSH in diabetic rat hearts and prevented apoptosis. Our data suggest for the first time that mGSH is crucial for modulating the cell suicide program in short-term diabetic rat hearts.

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Selective retroinfusion of GSH and cariporide attenuates myocardial ischemia–reperfusion injury in a preclinical pig model

Cited by 31 publications

References 43 publications

The Role of Oxidative Stress in Myocardial Ischemia and Reperfusion Injury and Remodeling: Revisited

The Role of Oxidative Stress in Myocardial Ischemia and Reperfusion Injury and Remodeling: Revisited

Mechanism of the Protective Effect of Yulangsan Flavonoid on Myocardial Ischemia/Reperfusion Injury in Rats

Cardiomyocyte apoptosis induced by short-term diabetes requires mitochondrial GSH depletion

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