Effect of ozone treatment on reactive oxygen species and adenosine production during hepatic ischemia-reperfusion.
This study investigates whether ozone could confer protection from hepatic ischemia reperfusion by modifying the accumulation of adenosine and xanthine during ischemia. A significant increase in both adenosine and xanthine accumulation was observed as a consequence of ATP degradation during hepatic ischemia. Adenosine exerts a protective effect on hepatic ischemia reperfusion injury since the elimination of endogenous adenosine accumulation with adenosine deaminase increased the hepatic injury associated with this process. On the other hand, the high xanthine levels observed after ischemia could exert deleterious effects during reperfusion due to reactive oxygen species generation from xanthine oxidase. The administration of allopurinol, an inhibitor of xanthine oxidase, attenuated the increase in reactive oxygen species and transaminase levels observed after hepatic reperfusion. Ozone treatment in liver maintained adenosine levels similar to those found after ischemia but led to a marked reduction in xanthine accumulation. In order to evaluate the role of both adenosine and xanthine, we tried to modify the protection confered by ozone, by modifying the concentrations of adenosine and xanthine. The metabolization of endogenous adenosine after ischemia abolished the protective effect conferred by ozone. When xanthine was administered previous to ozone treatment, the protection conferred by adenosine disappeared, showing both postischemic reactive oxygen species and transaminase levels similar to those found after hepatic ischemia reperfusion. Ozone would confer protection against the hepatic ischemia reperfusion injury by the accumulation of adenosine that in turns benefits the liver and by blocking the xanthine/xanthine oxidase pathway for reactive oxygen species generation.
Peralta
C
C
Department of Medical Bioanalysis, Instituto de Investigaciones Biomédicas de Barcelona, CSIC-IDIBAPS, Barcelona, Spain.
Xaus
C
C
Bartrons
R
R
Leon
O S
OS
Gelpi
E
E
Roselló-Catafau
J
J
D000241:Adenosine / Q000096:biosynthesis* / Q000378:metabolism; D000818:Animals; D007511:Ischemia / Q000378:metabolism*; D008099:Liver / Q000098:blood supply*; D008297:Male; D010126:Ozone / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015427:Reperfusion Injury / Q000378:metabolism / Q000517:prevention & control*; D019820:Xanthine / Q000378:metabolism
D017382:Reactive Oxygen Species; D019820:Xanthine; D010126:Ozone; D000241:Adenosine