Effects of inosine on reperfusion injury after cardiopulmonary bypass

Veres, Gábor; Radovits, Tamás; Serés, L.; Horkay, Ferenc; Kretzler, Matthias; Szabó, Gábor

doi:10.1186/1749-8090-5-106

Cited by 8 publications

(3 citation statements)

References 30 publications

(30 reference statements)

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“…Inosine increases neuronal survival and neurite outgrowth in vitro , enhances axon regeneration and axonal sprouting after damage of the central nervous system, and promotes recovery in rodent models of stroke and focal brain trauma 1 2 3 . Administration of inosine improves myocardial function during acute left ventricular failure and protects myocardial and endothelial function after heart transplantation 4 5 . Inosine also augments mast-cell degradation, suppresses macrophage, lymphocyte and neutrophil activation, and attenuates inflammatory diseases 6 7 .…”

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confidence: 99%

Oral administration of inosine produces antidepressant-like effects in mice

Muto

Lee

et al. 2014

Sci Rep

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Inosine, a breakdown product of adenosine, has recently been shown to exert immunomodulatory and neuroprotective effects. We show here that the oral administration of inosine has antidepressant-like effects in two animal models. Inosine significantly enhanced neurite outgrowth and viability of primary cultured neocortical neurons, which was suppressed by adenosine A1 and A2A receptor agonists. Oral administration of inosine to mice transiently increased its concentration in the brain and enhanced neuronal proliferation in the dentate gyrus, accompanied by phosphorylation of mitogen-activated protein kinase and increase in transcript level of brain-derived neurotrophic factor. In stress models, oral inosine prevented an increase in immobility time in forced swim test after chronically unexpected stress and mitigated a reduction in sucrose preference after chronic social defeat stress. These results indicate that oral administration of inosine has the potential to prevent depressive disorder via adenosine receptors.

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confidence: 99%

Oral administration of inosine produces antidepressant-like effects in mice

Muto

Lee

et al. 2014

Sci Rep

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“…While the therapeutic utilization of adenosine as a hepatoprotective agent in vivo is difficult due to its short half-life and adverse cardiovascular side-effect profile, inosine may emerge as a potential candidate. Indeed, several recent studies have demonstrated that administration of inosine can be protective against various forms of ischemic conditions ( 7 – 10 ). The current results may provide a mechanistic explanation to the previously reported protective effect of inosine in vitro as an adjuvant to organ storage solutions ( 47 ) or in vivo as a protective agent in a rat model of hepatic reperfusion injury ( 48 ) and can stimulate further studies to explore whether inosine has the potential to improve cellular bioenergetics and to protect hepatocytes in various forms of liver injury, including various forms of warm ischemia or cold ischemia associated with liver transplantation.…”

Section: Discussionmentioning

confidence: 99%

“…For a long time inosine was considered to be an inactive metabolite. However, several studies have shown that it has immunomodulatory, neuroprotective, cardioprotective and cytoprotective effects ( 7 – 10 ). These effects have been attributed to several independent mechanisms.…”

Section: Introductionmentioning

confidence: 99%

Adenosine and inosine exert cytoprotective effects in an in vitro model of liver ischemia-reperfusion injury

Módis

Gerö

Stangl

et al. 2012

International Journal of Molecular Medicine

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Liver ischemia represents a common clinical problem. In the present study, using an in vitro model of hepatic ischemia-reperfusion injury, we evaluated the potential cytoprotective effect of the purine metabolites, such as adenosine and inosine, and studied the mode of their pharmacological actions. The human hepatocellular carcinoma-derived cell line HepG2 was subjected to combined oxygen-glucose deprivation (COGD; 0-14-24 h), followed by re-oxygenation (0-4-24 h). Adenosine or inosine (300–1,000 μM) were applied in pretreatment. Cell viability and cytotoxicity were measured by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide and lactate dehydrogenase methods, respectively. The results showed that both adenosine and inosine exerted cytoprotective effects, and these effects were not related to receptor-mediated actions, since they were not prevented by selective adenosine receptor antagonists. On the other hand, the adenosine deaminase inhibitor erythro-9-(2-hydroxy-3-nonyl) adenine hydrochloride (EHNA, 10 μM) markedly and almost fully reversed the protective effect of adenosine during COGD, while it did not influence the cytoprotective effect of inosine in the same assay conditions. These results suggest that the cytoprotective effects are related to intracellular actions, and, in the case of adenosine also involve intracellular conversion to inosine. The likely interpretation of these findings is that inosine serves as an alternative source of energy to produce ATP during hypoxic conditions. The protective effects are also partially dependent on adenosine kinase, as the inhibitor 4-amino-5-(3-bromophenyl)-7-(6-morpholino-pyridin-3-yl)pyrido[2,3-d]pyrimidine, 2HCl (ABT 702, 30 μM) significantly reversed the protective effect of both adenosine and inosine during hypoxia and re-oxygenation. Collectively, the current results support the view that during hypoxia, adenosine and inosine exert cytoprotective effects via receptor-independent, intracellular modes of action, which, in part, depend on the restoration of cellular bioenergetics. The present study supports the view that testing of inosine for protection against various forms of warm and cold liver ischemia is relevant.

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