Effects of inosine on reperfusion injury after heart transplantation☆

Szabó, Gábor; Stumpf, Nicole; Radovits, Tamás; Sonnenberg, Karin; Gerö, Domokos; Hagl, S.; Szabó, Csaba; Bährle, Susanne

doi:10.1016/j.ejcts.2006.04.003

Cited by 33 publications

(25 citation statements)

References 23 publications

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“…Additionally, nucleosides function as extracellular signalling molecules and, although inosine is only present at low levels in the extracellular space, metabolically stressful conditions such as nflammation dramatically increase the concentration (Hasko et al 2004). Inosine has proved to be a powerful immunomodulatory agent both in vitro (Hasko et al 2000 and in vivo (Hasko et al 2000, Garcia Soriano et al 2001, Mabley et al 2003a,b, Darlington & Gann 2005, Schneider & Klein 2005, Szabo et al 2006. Inosine treatment reduces the production of inflammatory cytokines by murine and human macrophages stimulated by lipopolysaccharide (LPS) in addition to the provided protective effects on both intestinal and vascular function in murine models of endotoxic shock (Hasko et al 2000, Garcia Soriano et al 2001.…”

Section: Introductionmentioning

confidence: 99%

The novel inosine analogue, INO-2002, protects against diabetes development in multiple low-dose streptozotocin and non-obese diabetic mouse models of type I diabetes

Mabley

Pacher

Murthy

et al. 2008

Journal of Endocrinology

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Endogenous purines including inosine have been shown to exert immunomodulatory and anti-inflammatory effects in a variety of disease models. The dosage of inosine required for protection is very high because of the rapid metabolism of inosine in vivo. The aim of this study was to determine whether a metabolic-resistant purine analogue, INO-2002, exerts antiinflammatory effects in two animal models of type I diabetes.

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Section: Introductionmentioning

confidence: 99%

The novel inosine analogue, INO-2002, protects against diabetes development in multiple low-dose streptozotocin and non-obese diabetic mouse models of type I diabetes

Mabley

Pacher

Murthy

et al. 2008

Journal of Endocrinology

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“…Until recently, inosine was considered an inactive purine metabolite in most biological systems, but several recent studies have shown that it has immuno-modulatory [10], neuroprotective [11], cardioprotective [12] and overall cytoprotective effects. Furthermore, some other studies reported that extracellular inosine has powerful cellular protective effects.…”

Section: Discussionmentioning

confidence: 99%

“…For example, inosine decreases the release of intracellular enzymes from hypoxic lymphocytes [13], improves renal function during ischemia [14] and inhibits inflammatory cytokine production [7]. Administration of inosine has also been shown to improve myocardial function during acute left ventricular failure [15,16] and improve myocardial and endothelial function after heart transplantation [12]. Despite the growing evidence of protective effects of inosine, the use of inosine for prevention of reperfusion injury in the context of cardiopulmonary bypass has not yet been investigated.…”

Section: Discussionmentioning

confidence: 99%

Effects of inosine on reperfusion injury after cardiopulmonary bypass

Veres

Radovits

Serés

et al. 2010

J Cardiothorac Surg

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ObjectiveInosine, a break-down product of adenosine has been recently shown to exert inodilatory and anti-inflammatory properties. Furthermore inosine might be a key substrate of pharmacological post-conditioning. In the present pre-clinical study, we investigated the effects of inosine on cardiac function during reperfusion in an experimental model of cardioplegic arrest and extracorporal circulation.MethodsTwelve anesthetized dogs underwent hypothermic cardiopulmonary bypass. After 60 minutes of hypothermic cardiac arrest, reperfusion was started after application of either saline vehicle (control, n = 6), or inosine (100 mg/kg, n = 6). Left ventricular end-systolic pressure volume relationship (ESPVR) was measured by a combined pressure-volume-conductance catheter at baseline and after 60 minutes of reperfusion. Left anterior descendent coronary blood flow (CBF), endothelium-dependent vasodilatation to acetylcholine (ACh) and endothelium-independent vasodilatation to sodium nitroprusside (SNP) were also determined.ResultsThe administration of inosine led to a significantly better recovery (given as percent of baseline) of ESPVR 90 ± 9% vs. 46 ± 6%, p < 0.05. CBF and was also significantly higher in the inosine group (56 ± 8 vs. 23 ± 4, ml/min, p < 0.05). While the vasodilatatory response to SNP was similar in both groups, ACh resulted in a significantly higher increase in CBF (58 ± 6% vs. 25 ± 5%, p < 0.05) in the inosine group.ConclusionsApplication of inosine improves myocardial and endothelial function after cardiopulmonary bypass with hypothermic cardiac arrest.

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“…For instance, inosine can stimulate degranulation of mast cell (Jin et al 1997), inhibit the activation of human neutrophils (Marton et al 2001), reduce the production of proinflammatory cytokines tumor necrosis factor-alpha, interleukin-1, interleukin-12, and counteract the inflammatory response induced by endotoxin (Hasko et al 2000;Liaudet et al 2002). Inosine also may attenuate ischemia-reperfusion injury in the rat heart transplantation model (Szabo et al 2006).…”

Section: Introductionmentioning

confidence: 98%

The Protective Effects of Inosine Against Chemical Hypoxia on Cultured Rat Oligodendrocytes

Yang

Zhao

et al. 2011

Cell Mol Neurobiol

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Inosine is a purine nucleoside and is considered protective to neural cells including neurons and astrocytes against hypoxic injury. However, whether oligodendrocytes (OLs) could also be protected from hypoxia by inosine is not known. Here we investigated the effects of inosine on primarily cultured rat OLs injured by rotenone-mediated chemical hypoxia, and the mechanisms of the effects using ATP assay, MTT assay, PI-Hoechst staining, TUNEL, and immunocytochemistry. Results showed that rotenone exposure for 24 h caused cell death and impaired viability in both immature and mature OLs, while pretreatment of 10 mM inosine 30 min before rotenone administration significantly reduced cell death and improved the viability of OLs. The same concentration of inosine given 120 min after rotenone exposure also improved viability of injured mature OLs. Immunocytochemistry for nitrotyrosine and cellular ATP content examination indicated that inosine may protect OLs by providing ATP and scavenging peroxynitrite for cells. In addition, immature OLs were more susceptible to hypoxia than mature OLs; and at the similar degree of injury, inosine protected immature and mature OLs differently. Quantitative real-time PCR revealed that expression of adenosine receptors was different between these two stages of OLs. These data suggest that inosine protect OLs from hypoxic injury as an antioxidant and ATP provider, and the protective effects of inosine on OLs vary with cell differentiation, possibly due to the adenosine receptors expression profile. As OLs form myelin in the central nervous system, inosine could be used as a promising drug to treat demyelination-involved disorders.

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Effects of inosine on reperfusion injury after heart transplantation☆

Cited by 33 publications

References 23 publications

The novel inosine analogue, INO-2002, protects against diabetes development in multiple low-dose streptozotocin and non-obese diabetic mouse models of type I diabetes

The novel inosine analogue, INO-2002, protects against diabetes development in multiple low-dose streptozotocin and non-obese diabetic mouse models of type I diabetes

Effects of inosine on reperfusion injury after cardiopulmonary bypass

The Protective Effects of Inosine Against Chemical Hypoxia on Cultured Rat Oligodendrocytes

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