Ozone oxidative preconditioning is mediated by A₁adenosine receptors in a rat model of liver ischemia/ reperfusion

Abstract

Summary The liver is damaged by sustained ischemia in liver transplantation, and the reperfusion after ischemia results in further functional impairment. Ozone oxidative preconditioning (OzoneOP) protected the liver against ischemia/reperfusion (I/R) injury. The aim of this study was to investigate the role of A1 adenosine receptor on the protective actions conferred by OzoneOP in hepatic I/R. By using a specific agonist and antagonist of the A1 subtype receptor (2‐chloro N6 cyclopentyladenosine, CCPA and 8‐cyclopentyl‐1,3‐dipropylxanthine, DPCPX respectively), we studied the role of A1 receptor in the protective effects of OzoneOP on the liver damage, nitiric oxide (NO) generation, adenosine deaminase activity and preservation of the cellular redox balance. Immunohistochemical analysis of nuclear factor‐kappa B (NF‐κB), tumor necrosis factor alpha (TNF‐α) and heat shock protein‐70 (HSP‐70) was performed. OzoneOP prevented and/or ameliorated ischemic damage. CCPA showed a similar effect to OzoneOP + I/R group. A1AR antagonist DPCPX blocked the protective effect of OzoneOP. OzoneOP largely reduced the intensity of the p65 expression, diminished TNF‐α production, and promoted a reduction in HSP‐70 immunoreactivity. In summary, OzoneOP exerted protective effects against liver I/R injury through activation of A1 adenosine receptors (A1AR). Adenosine and .NO produced by OzoneOP may play a role in the pathways of cellular signalling which promote preservation of the cellular redox balance, mitochondrial function, glutathione pools as well as the regulation of NF‐κB and HSP‐70.

Purinergic Signaling and Blood Vessels in Health and Disease

“…However, administration of an adenosine A 1 receptor antagonist before ischemia attenuates ischemia-reperfusion injury (Magata et al, 2007;Kim et al, 2008). Ozone oxidative preconditioning is mediated by A 1 receptors in a rat model of liver ischemia-reperfusion (León Fernández et al, 2008). Selective intrarenal human A 1 receptor overexpression reduced acute liver (and kidney) injury after hepatic ischemia-reperfusion in mice (Park et al, 2010b).…”

Ischaemic and pharmacological preconditionings protect liver via adenosine and redox status following hepatic ischaemia/reperfusion in rats

“…Peralta et al [14] and others [15] have demonstrated that hepatoprotection induced by IPC is mediated by the activation of A 2 R. Although, Schauer et al [16] reported no evidence for a role of A 2 R in the cytoprotective effects of IPC, they suggested the implication of other adenosine receptor subclasses or additional mediators of IPC that could play a role in such settings. Recently, we have reported that the protective effects of oxidative preconditioning in liver are mediated by the activation of A 1 R by CCPA [17]. Moreover, experimental evidence demonstrates the involvement of A 1 R in other organs [12,13,[18][19][20].…”

Purinergic signalling in the liver in health and disease

“…Administration of an adenosine A 1 receptor antagonist before ischaemia attenuated ischaemia-reperfusion injury [153,169]. Oxidative preconditioning by ozone was mediated by A 1 receptors in a rat model of liver ischaemia reperfusion [163].…”