Carvedilol protects tubular epithelial cells from ischemia–reperfusion injury by inhibiting oxidative stress

Hayashi, Taiji; Velasco, Marco A. De; Saitou, Yoshitaka; Nose, Kazuhiro; Nishioka, Tsukasa; Ishii, Tokumi; Uemura, Hirotsugu

doi:10.1111/j.1442-2042.2010.02644.x

Cited by 35 publications

(35 citation statements)

References 22 publications

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“…24 Indeed, peroxidation of membrane lipids can disrupt membrane fluidity and cell compartmentalization, which can result in cell lysis. 4 Numerous studies concerning the renoprotective effects of TMZ have been well documented. 12,13,25 It is recognized that TMZ has antioxidant effects and its role in lipid peroxidation inhibition has been well established in different organs.…”

Section: Discussionmentioning

confidence: 99%

“…3,5 The excessive ROS generation induces lipid peroxidation, inactivation of antioxidant enzymes, disruptions of the cellular cytoskeleton and cellular integrity, DNA breakdown and endothelial cell damage. 2,4 These factors contribute to cell death and tissue damage. 6 Cellular defense against ROS induced by I/R is provided by enzymatic (catalase, superoxide dismutase, and glutathione peroxidase) and non-enzymatic (alpha tocopherol, glutathione (GSH), ascorbic acid, carotene, etc) antioxidant systems.…”

Section: Introductionmentioning

confidence: 99%

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Effects of trimetazidine on the Akt/eNOS signaling pathway and oxidative stress in anin vivorat model of renal ischemia-reperfusion

et al. 2014

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Renal ischemia reperfusion (I/R) injury, which occurs during renal surgery or transplantation, is the major cause of acute renal failure. Trimetazidine (TMZ), an anti-ischemic drug, protects kidney against the deleterious effects of I/R. However its protective mechanism remains unclear. The aim of this study is to examine the relevance of Akt, endothelial nitric oxide synthase (eNOS), and hypoxia inducible factor-1a (HIF-1a) on TMZ induced protection of kidneys against I/R injury. Wistar rats were subjected to 60 min of warm renal ischemia followed by 120 min of reperfusion, or to intraperitoneal injection of TMZ (3 mg/kg) 30 min before ischemia. In sham operated group renal pedicles were only dissected. Compared to I/R, TMZ treatment decreased lactate dehydrogenase (845 ± 13 vs. 1028 ± 30 U/L). In addition, creatinine clearance and sodium reabsorption rates reached 105 ± 12 versus 31 ± 11 mL/min/g kidney weight and 95 ± 1 versus 68 ± 5%, respectively. Besides, we noted a decrease in malondialdehyde concentration (0.33 ± 0.01 vs. 0.59 ± 0.03 nmol/mg of protein) and an increase in glutathione concentration (2.6 ± 0.2 vs. 0.93 ± 0.16 mg GSH/mg of protein), glutathione peroxidase (95 ± 4 vs. 61 ± 3 mg GSH/min/mg of protein), and superoxide dismutase (25 ± 3 vs. 11 ± 2 U/mg of protein) and catalase (91 ± 12 vs. 38 ± 9 mmol/min/mg of protein) activities. Parallely, we noted a significant increase in p-Akt, eNOS, nitrite and nitrate (18 ± 2 vs. 8 ± 0.1 pomL/mg of protein), HIF-1a (333 ± 48 vs. 177 ± 14 mg/mg of protein) and heme oxygenase-1 (HO-1) levels regarding I/R. TMZ treatment improves renal tolerance to warm I/R. Such protection implicates an activation of Akt/eNOS signaling pathway, HIF-1a stabilization and HO-1 activation.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Effects of trimetazidine on the Akt/eNOS signaling pathway and oxidative stress in anin vivorat model of renal ischemia-reperfusion

et al. 2014

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“…These data showed the potential benefit of Carv pretreatment to decrease the apoptosis of transplanted cells. We speculate that through Carv's dual properties as a ␤-blocker and antioxidant, it maintains a unique ability to restore cardiac function and scavenge superoxide radicals (Hayashi et al, 2010). These dual properties of Carv distinguish it from drugs with only antioxidant properties.…”

Section: Carvedilol Enhances Stem Cell Therapy For MI 65mentioning

confidence: 99%

Carvedilol Enhances Mesenchymal Stem Cell Therapy for Myocardial Infarction via Inhibition of Caspase-3 Expression

Hassan

Meduru

Taguchi

et al. 2012

J Pharmacol Exp Ther

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Adult stem cells have shown great promise toward repairing infarcted heart and restoring cardiac function. Mesenchymal stem cells (MSCs), because of their inherent multipotent nature and their ability to secrete a multitude of growth factors and cytokines, have been used for cardiac repair with encouraging results. Preclinical studies showed that MSCs injected into infarcted hearts improve cardiac function and attenuate fibrosis. Although stem cell transplantation is a promising therapeutic option to repair the infarcted heart, it is faced with a number of challenges, including the survival of the transplanted cells in the ischemic region, due to excessive oxidative stress present in the ischemic region. The objective of this study was to determine the effect of Carvedilol (Carv), a nonselective ␤-blocker with antioxidant properties, on the survival and engraftment of MSCs in the infarcted heart. MSCs were subjected to a simulated host-tissue environment, similar to the one present in the infarcted myocardium, by culturing them in the presence of hydrogen peroxide (H 2 O 2 ) to induce oxidative stress. MSCs were treated with 2.5 M Carv for 1 h in serum-free medium, followed by treatment with H 2 O 2 for 2 h. The treated cells exhibited significant protection against H 2 O 2 -induced cell death versus untreated controls as determined by 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assays. Likewise, transplantation of MSCs after permanent left coronary artery ligation and treatment of animals after myocardial infarction (MI) with Carv (5 mg/kg b.wt.) led to significant improvement in cardiac function, decreased fibrosis, and caspase-3 expression compared with the MI or MSC-alone groups.

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“…is a third-generation vasodilator agent used in the treatment of hypertension, ischemic heart disease and congestive heart failure (102)(103)(104). It selectively blocks α1-receptors and non-selectively blocks β1 and β2-adrenoceptors (102).…”

Section: Carvedilol (Cvdmentioning

confidence: 99%

Medical perspective in testicular ischemia-reperfusion injury

Arena

Iacona

Antonuccio

et al. 2017

Experimental and Therapeutic Medicine

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Abstract. Testicular torsion or torsion of the spermatic cord is one of the most serious urological conditions. It causes testicular injury, which potentially leads to male subfertility. The turning of the spermatic cord and spermatic structures around themselves results in biochemical and histological changes; however, following testicular detorsion, tissues undergo reperfusion that causes more severe damage than that induced by ischemia. Since the primary causes of testicular damage are reactive oxygen species production, an increase in intra-mitochondrial calcium concentration and an increased rate of cellular apoptosis, different medications may potentially be effective. It seems that several medications, experimentally and sometimes clinically, serve an adjuvant role in the cellular damage that occurs following ischemia-reperfusion. Antioxidants, calcium channel blockers, phytotherapeutical medicinals, anaesthetics, hormones and platelet inhibitors may potentially create a solid basis for an adjuvant restoring therapy and ameliorate testicular function following torsion. The current study aimed to review the relevant literature and discuss the actions of a number of molecules that may protect the testes during ischemia/reperfusion injury.

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Carvedilol protects tubular epithelial cells from ischemia–reperfusion injury by inhibiting oxidative stress

Cited by 35 publications

References 22 publications

Effects of trimetazidine on the Akt/eNOS signaling pathway and oxidative stress in anin vivorat model of renal ischemia-reperfusion

Effects of trimetazidine on the Akt/eNOS signaling pathway and oxidative stress in anin vivorat model of renal ischemia-reperfusion

Carvedilol Enhances Mesenchymal Stem Cell Therapy for Myocardial Infarction via Inhibition of Caspase-3 Expression

Medical perspective in testicular ischemia-reperfusion injury

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