8‐Br‐cADPR, a TRPM2 ion channel antagonist, inhibits renal ischemia–reperfusion injury

Eraslan, Ersen; Tanyeli, Ayhan; Polat, Elif

doi:10.1002/jcp.27236

Cited by 39 publications

(29 citation statements)

References 78 publications

(124 reference statements)

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“…It is worth noting that inhibitors identified in earlier studies, including 2-aminoethoxydiphenyl borate (2-APB), N-( p -amycinnamoyl) anthranilic acid (ACA), antifungal agents such as clotrimazole (CTZ) and econazole and the non-steroidal anti-inflammatory flufenamic acid (FFA), while inhibiting the TRPM2 channel with concentrations producing a 50% inhibition (IC 50 ) in the range of μM ( Table 2 ) [ [106] , [107] , [108] , [109] , [110] , [111] ], lack specificity towards the TRPM2 channel [ 73 ]. 8-Br-cADPR, an ADPR analogue, is reported to inhibit the TRPM2 channel by in vitro [ 62 ] and also in vivo studies [ 112 ] but, of notice, its inhibition has not been consistently observed [ 113 ]. Recent studies have tested various other ADPR-related analogues for their potential to selectively inhibit the TRPM2 channel in vitro [ 114 , 115 ], identifying multiple compounds such as 8-phenyl-2′-deoxy-ADPR, 7i and 8a ( Table 2 ).…”

Section: Trpm2 Channel Properties Activation Mechanisms and Pharmacmentioning

confidence: 99%

“…Such kidney damage and loss of function in WT mice were also reduced in mice injected with 2-APB prior to ischemia or after reperfusion. A more recent study has reported that I/R-induced kidney damage examined histologically using H&E staining in WT mice was prevented by treatment with 8-Br-cADPR to antagonise TRPM2 channel activation [ 112 ]. These studies provide consistent evidence to support an important role for the TRPM2 channel in I/R-induced acute kidney injury.…”

Section: Trpm2 In Kidney Cell Death Associated With Acute Kidney Injumentioning

confidence: 99%

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TRPM2 channel-mediated cell death: An important mechanism linking oxidative stress-inducing pathological factors to associated pathological conditions

Malko

Jiang

2020

Redox Biology

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Oxidative stress resulting from the accumulation of high levels of reactive oxygen species is a salient feature of, and a well-recognised pathological factor for, diverse pathologies. One common mechanism for oxidative stress damage is via the disruption of intracellular ion homeostasis to induce cell death. TRPM2 is a non-selective Ca 2+ -permeable cation channel with a wide distribution throughout the body and is highly sensitive to activation by oxidative stress. Recent studies have collected abundant evidence to show its important role in mediating cell death induced by miscellaneous oxidative stress-inducing pathological factors, both endogenous and exogenous, including ischemia/reperfusion and the neurotoxicants amyloid-β peptides and MPTP/MPP + that cause neuronal demise in the brain, myocardial ischemia/reperfusion, proinflammatory mediators that disrupt endothelial function, diabetogenic agent streptozotocin and diabetes risk factor free fatty acids that induce loss of pancreatic β-cells, bile acids that damage pancreatic acinar cells, renal ischemia/reperfusion and albuminuria that are detrimental to kidney cells, acetaminophen that triggers hepatocyte death, and nanoparticles that injure pericytes. Studies have also shed light on the signalling mechanisms by which these pathological factors activate the TRPM2 channel to alter intracellular ion homeostasis leading to aberrant initiation of various cell death pathways. TRPM2-mediated cell death thus emerges as an important mechanism in the pathogenesis of conditions including ischemic stroke, neurodegenerative diseases, cardiovascular diseases, diabetes, pancreatitis, chronic kidney disease, liver damage and neurovascular injury. These findings raise the exciting perspective of targeting the TRPM2 channel as a novel therapeutic strategy to treat such oxidative stress-associated diseases.

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Section: Trpm2 Channel Properties Activation Mechanisms and Pharmacmentioning

confidence: 99%

Section: Trpm2 In Kidney Cell Death Associated With Acute Kidney Injumentioning

confidence: 99%

TRPM2 channel-mediated cell death: An important mechanism linking oxidative stress-inducing pathological factors to associated pathological conditions

Malko

Jiang

2020

Redox Biology

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“…Studies involving both abdominal and renal I/R models have reported that I/R causes apoptosis in renal tubule cells [11,27] . In their study using an aortic cross-clamping model in rats, Cüre et al [10] reported an increase in Caspase-3 positivity in apoptotic renal cells following I/R application.…”

Section: Discussionmentioning

confidence: 99%

The Role of Vaccinium Myrtillus in the Prevention of Renal Injury in an Experimental Model of Ruptured Abdominal Aortic Aneurysm

Ergene¹,

Hemsinli²,

Karakişi³

et al. 2020

Braz J Cardiovasc Surg

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Objective: To examine the biochemical and histopathological renal effects of ischemia/reperfusion (I/R) injury using a ruptured abdominal aortic aneurysm (RAAA) model in rats and to investigate the potential protective effects of whortleberry (Vaccinium myrtillus). Methods: Thirty-two male Sprague-Dawley rats were randomly assigned into four groups-control, sham (I/R+glycerol), I/R, and I/ R+whortleberry. Midline laparotomy alone was performed in the control group. Atraumatic abdominal clamps were attached under anesthesia to the abdominal aorta beneath the level of the renal artery in the groups subjected to I/R. Sixty-minute reperfusion was established one hour after ischemia. The sham group received five intraperitoneal doses of glycerol five days before I/R. The I/ R+whortleberry group received a single intraperitoneal 50 mg/kg dose diluted with saline solution five days before I/R. All animals were finally euthanized by cervical dislocation following 60-min reperfusion. Results: Increases were observed in malondialdehyde (MDA) levels and tubular necrosis scores (TNS) in thin kidney tissues and in numbers of apoptotic renal tubule cells, together with a decrease in glutathione (GSH) levels, in sham and I/R groups. In contrast, we observed a decrease in MDA levels, TNS, and numbers of apoptotic renal tubule cells, and an increase in GSH levels with whortleberry treatment compared to the I/R group. Conclusion: Our findings suggest that whortleberry may be effective against acute kidney injury by reducing oxidative stress and apoptosis.

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“…Although organ reperfusion following ischemia may decrease the existing injury, it may adversely affect several cellular processes emerging due to the reperfusion. The severity of the injury may lead to organ dysfunctions [2,3]. Hypoxia, inflammatory cytokines, and free oxygen radicals are the underlying factors of the renal IRI.…”

Section: Introductionmentioning

confidence: 99%

Ratlarda böbrek iskemi-reperfüzyon hasarında proflaktik kalsiyum dobesilatın etkinliği

Akkoç¹,

Metin

2020

Acta Medica Alanya

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Amaç: Çalışmamızda, antioksidan ve antienflamatuvar özellikleri olduğu bilinen, kalsiyum dobesilatın deneysel böbrek iskemi-reperfüzyon hasarı (IRI) üzerindeki koruyucu etkisini araştırmayı amaçladık. Yöntemler: 24 adet erkek Wistar-Albino rat üç gruba ayrıldı; sham grubu (grup 1), iskemi-reperfüzyon grubu (grup 2) ve tedavi grubu (grup 3). İskemi-reperfüzyon işlemi öncesi Grup 3'e 10 gün boyunca 100 mg/kg/gün kalsiyum dobesilat gavaj yolu ile verildi. Sham grubu haricindeki gruplara 45 dakika iskemi ve 24 saat reperfüzyon uygulandı. Plazma üre ve kreatinin düzeyleri, eritrosit süperoksit dismutaz ve glutatyon peroksidaz enzim aktivite düzeyleri çalışıldı. Ayrıca böbrek dokusundaki iskemi-reperfüzyon hasırına ait olabilecek histopatolojik değişiklikler incelendi. Bulgular: Grup 2'de ortanca glutatyon peroksidaz ve süperoksit dismutaz enzim düzeyleri Grup 1 ve Grup 3'den daha yüksekti, ancak istatistiksel anlamlı değildi. Grup 3'de kreatinin düzeyleri Grup 1 ve Grup 2'den istatistiksel olarak anlamlı derecede daha düşüktü. Ortanca üre değerleri Grup 3'de Grup 1 ve Grup 2'den daha düşüktü ancak istatistiksel olarak anlamlı değildi. Histopatolojik incelemede; kontrol grubu ile kıyaslandığında tedavi grubunda, hücre nekrozu, tübüler epitelyal hücre düzleşmesi, sitoplazmik vakuolizasyon, tübüler lümen obstrüksiyonu ve kronik inflamasyon gibi iskemi-reperfüzyon hasarının göstergesi olan bu parametrelerin istatistiksel olarak anlamlı derecede daha az olduğu gözlendi. Sonuç: Çalışmamız, proflaktik kalsiyum dobesilatın böbrek iskemi-reperfüzyon hasarında koruyucu etkilerinin olduğunu göstermiştir.

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8‐Br‐cADPR, a TRPM2 ion channel antagonist, inhibits renal ischemia–reperfusion injury

Cited by 39 publications

References 78 publications

TRPM2 channel-mediated cell death: An important mechanism linking oxidative stress-inducing pathological factors to associated pathological conditions

TRPM2 channel-mediated cell death: An important mechanism linking oxidative stress-inducing pathological factors to associated pathological conditions

The Role of Vaccinium Myrtillus in the Prevention of Renal Injury in an Experimental Model of Ruptured Abdominal Aortic Aneurysm

Ratlarda böbrek iskemi-reperfüzyon hasarında proflaktik kalsiyum dobesilatın etkinliği

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