Oral Pretreatment with Ebselen Enhances Heat Shock Protein 72 Expression and Reduces Myocardial Infarct Size

Baljinnyam, Erdenechimeg; Hasebe, Naoyuki; Morihira, Masahiko; Sumitomo, Kazuhiro; Matsusaka, Tomoyuki; Fujino, Takayuki; Fukuzawa, Jun; Ushikubi, Fumitaka; Kikuchi, Kenjiro

doi:10.1291/hypres.29.905

Cited by 34 publications

(21 citation statements)

References 45 publications

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“…Oral intake pretreatment with ebselen enhances HSP72 expression and reduces ROS induced by I/R injury (Baljinnyam et al 2006). To determine if increased levels of HSP70 might contribute to the induction of antioxidant pathways, which detoxify ROS, we measured the activities of antioxidant enzymes and lipid peroxidation in heart homogenates.…”

Section: Discussionmentioning

confidence: 99%

Lipopolysaccharide pretreatment protects against ischemia/reperfusion injury via increase of HSP70 and inhibition of NF-κB

Yao

Zhang

et al. 2011

Cell Stress and Chaperones

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It has been reported that pretreatment of rats with lipopolysaccharide (LPS) increases myocardial functional recovery in ischemia/reperfusion (I/R) hearts. However, the mechanisms by which LPS induces cardioprotection against I/R injury have not been fully elucidated. In this study, we pretreated rats with LPS (1.0 mg/kg) 24 h before they were subjected to I/R injury, and then examined the roles of heat shock protein-70 (HSP70) and nucleus factor-κB (NF-κB) in LPS-induced cardioprotection. We observed that pretreatment with low-dose LPS resulted in significantly increased levels of HSP70 in the myocardium, which could dramatically inhibit NF-κB translocation and reduce degradation of inhibitory κB. Inhibition of NF-κB, in turn, attenuated release of inflammatory cytokines (tumor necrosis factor-α, interleukin (IL)-1β, and IL-6) and reduced apoptosis of myocardium and infarct area following I/R injury. Moreover, HSP70 could ameliorate oxidative stress following I/R injury. To further investigate whether increase of HSP70 might be responsible for protection of the myocardium against I/R injury, we co-administered the HSP70 inhibitor, quercetin, with LPS before I/R injury. We found that LPS-induced cardioprotection was attenuated by co-administration with quercetin. Herein, we concluded that increased levels of HSP70 through LPS pretreatment led to inhibition of NF-κB activity in the myocardium after I/R injury. Our results indicated that LPS-induced cardioprotection was mediated partly through inhibition of NF-κB via increase of HSP70, and LPS pretreatment could provide a means of reducing myocardial I/R injury.

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Section: Discussionmentioning

confidence: 99%

Lipopolysaccharide pretreatment protects against ischemia/reperfusion injury via increase of HSP70 and inhibition of NF-κB

Yao

Zhang

et al. 2011

Cell Stress and Chaperones

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“…It has been shown that E could protect organs such as intestine, neurons, lungs, and myocardium against IRI. 6,[30][31][32] Taken together, E plays an important role in protection of kidneys against IRI experimentally. It may be a good candidate to prevent IRI in kidney transplantations but further studies should be conducted to evaluate its safety and efficacy in humans.…”

Section: Mda (Nmol/g-protein)mentioning

confidence: 98%

Beneficial Effects ofN-Acetylcysteine and Ebselen on Renal Ischemia/Reperfusion Injury

et al. 2011

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Introduction: It has been demonstrated that peroxynitrite accompanies acute renal ischemia and contributes to the pathophysiology of renal damage. Therefore, we aimed to investigate the roles of N-acetylcysteine (NAC), a well-known powerful antioxidant, and ebselen (E), a scavenger of peroxynitrite, on renal injury induced by renal ischemia/reperfusion injury (IRI) of rat kidney. Materials and methods: Forty male Sprague-Dawley rats were divided into five groups: sham, renal IRI, renal IRI+NAC, renal IRI+E, and renal IRI+NAC+E. IR injury was induced by 60 min of bilateral renal ischemia followed by 6 h of reperfusion. After reperfusion, kidneys and blood samples were obtained for histopathological and biochemical evaluations. Results: Renal IR resulted in increased malondialdehyde and nitrite/nitrate levels suggesting increased lipid peroxidation and peroxynitrite production and decreased superoxide dismutase and glutathione peroxidase activities. Both NAC and E alone significantly decreased malondialdehyde and nitrite/nitrate levels and increased superoxide dismutase and glutathione peroxidase activities. Additionally in the renal IRI+NAC+E group, all biochemical results were quite close to those of sham group. Histopathologically, the kidney injury in rats treated with combination of NAC and E was found significantly less than the other groups. Conclusions: Both NAC and E are able to ameliorate IRI of the kidney by decreasing oxidative and nitrosative stresses and increasing free radical scavenger properties. Additionally, combination of NAC and E prevents kidney damage more than when each drug is used alone, suggesting that scavenging peroxynitrite nearby antioxidant activity is important in preventing renal IRI.

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“…Particularly, the effects of oral administration of ebselen on experimental MI were examined by Baljinnyam et al [104] and quite remarkably, the enhancement of infarct size with H 2 O 2 was significantly attenuated in the ebselen30 group (P \ 0.01), and it was totally abolished in the ebselen100 group (P \ 0.05). It is also worth mentioning the decrease in myocardial 8-hydroxydeoxyguanosine (8-OHdG) levels as well as the increase in glutathione (GSH) levels after ebselen treatment.…”

Section: Novel Agentsmentioning

confidence: 98%

Conflicting effects of nitric oxide and oxidative stress in chronic heart failure: potential therapeutic strategies

Tousoulis

Papageorgiou²,

Briasoulis³

et al. 2011

Heart Fail Rev

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Chronic heart failure (CHF) is characterized by decreased nitric oxide (NO) bioavailability. In addition, the beneficial NO turns to be deleterious when it reacts with superoxide anion, leading to peroxynitrite formation. Numerous experimental and clinical studies have reported increased production of reactive oxygen species (superoxide, hydrogen peroxide, hydroxyl radical) both in animals and patients with CHF. Moreover, there are indicative data suggesting mechanisms associated with endothelial dysfunction in states of CHF, mainly attributed to decreased NO bioavailability and enhanced inactivation of the latter. Thus, such molecules appear to be potential targets in patients with CHF. These patients are strong candidates to receive a variety of therapeutic agents, some of which have known antioxidant effects. Classic treatment with statins or angiotensin converting enzyme inhibitors has been found to be beneficial in restoring NO and improving myocardial function and structure. Other agents such as sildenafil and b-blockers along with novel agents such as NO synthase transcription enhancers have been proved to be also beneficial, but their use for such a purpose is still controversial. Approaches using more-effective antioxidants or targeting myocardial oxidant-producing enzymes and oxidative or nitrosative stress might be promising strategies in the future.

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Oral Pretreatment with Ebselen Enhances Heat Shock Protein 72 Expression and Reduces Myocardial Infarct Size

Abstract: Reactive oxygen species (ROS) enhance myocardial ischemia-reperfusion (I/R

Cited by 34 publications

References 45 publications

Lipopolysaccharide pretreatment protects against ischemia/reperfusion injury via increase of HSP70 and inhibition of NF-κB

Lipopolysaccharide pretreatment protects against ischemia/reperfusion injury via increase of HSP70 and inhibition of NF-κB

Beneficial Effects ofN-Acetylcysteine and Ebselen on Renal Ischemia/Reperfusion Injury

Conflicting effects of nitric oxide and oxidative stress in chronic heart failure: potential therapeutic strategies

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