Ozone oxidative preconditioning is mediated by A1 adenosine receptors in a rat model of liver ischemia/ reperfusion.
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 A(1) adenosine receptor on the protective actions conferred by OzoneOP in hepatic I/R. By using a specific agonist and antagonist of the A(1) subtype receptor (2-chloro N6 cyclopentyladenosine, CCPA and 8-cyclopentyl-1,3-dipropylxanthine, DPCPX respectively), we studied the role of A(1) 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-kappaB), tumor necrosis factor alpha (TNF-alpha) 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. A(1)AR antagonist DPCPX blocked the protective effect of OzoneOP. OzoneOP largely reduced the intensity of the p65 expression, diminished TNF-alpha production, and promoted a reduction in HSP-70 immunoreactivity. In summary, OzoneOP exerted protective effects against liver I/R injury through activation of A(1) adenosine receptors (A(1)AR). 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-kappaB and HSP-70.
León Fernández
Olga S
OS
Center for Research and Biological Evaluation (CIEB-IFAL), University of Havana, Havana, Cuba.
Ajamieh
Hussam H
HH
Berlanga
Jorge
J
Menéndez
Silvia
S
Viebahn-Hánsler
Renate
R
Re
Lamberto
L
Carmona
Anna M
AM
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D058916:Adenosine A1 Receptor Antagonists; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D004195:Disease Models, Animal; D050884:HSP72 Heat-Shock Proteins / Q000378:metabolism; D007150:Immunohistochemistry; D019194:Ischemic Preconditioning / Q000379:methods*; D008099:Liver / Q000098:blood supply*; D016031:Liver Transplantation / Q000379:methods*; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis; D010083:Oxidants, Photochemical / Q000627:therapeutic use; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D010126:Ozone / Q000627:therapeutic use*; D058915:Purinergic P1 Receptor Antagonists; D051381:Rats; D017208:Rats, Wistar; D043682:Receptor, Adenosine A1 / Q000378:metabolism*; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014970:Xanthines / Q000494:pharmacology
D058916:Adenosine A1 Receptor Antagonists; D015415:Biomarkers; D050884:HSP72 Heat-Shock Proteins; D016328:NF-kappa B; D010083:Oxidants, Photochemical; D058915:Purinergic P1 Receptor Antagonists; D043682:Receptor, Adenosine A1; D014409:Tumor Necrosis Factor-alpha; D014970:Xanthines; D009569:Nitric Oxide; C058394:2-chloro-N(6)cyclopentyladenosine; D010126:Ozone; C051360:1,3-dipropyl-8-cyclopentylxanthine; D000241:Adenosine