Peralta C, Xaus C, Bartrons R, Leon O S, Gelpi E, Roselló-Catafau J
Department of Medical Bioanalysis, Instituto de Investigaciones Biomédicas de Barcelona, CSIC-IDIBAPS, Barcelona, Spain.
Free Radic Res. 2000 Nov;33(5):595-605. doi: 10.1080/10715760000301121.
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.
本研究调查臭氧是否可通过改变缺血期间腺苷和黄嘌呤的蓄积来对肝脏缺血再灌注起到保护作用。肝脏缺血期间，由于三磷酸腺苷（ATP）降解，腺苷和黄嘌呤的蓄积均显著增加。腺苷对肝脏缺血再灌注损伤具有保护作用，因为用腺苷脱氨酶消除内源性腺苷蓄积会增加与此过程相关的肝损伤。另一方面，缺血后观察到的高黄嘌呤水平可能在再灌注期间因黄嘌呤氧化酶产生活性氧而产生有害影响。给予黄嘌呤氧化酶抑制剂别嘌呤醇可减轻肝脏再灌注后观察到的活性氧增加和转氨酶水平升高。肝脏臭氧处理可使腺苷水平维持在与缺血后相似的水平，但导致黄嘌呤蓄积显著减少。为了评估腺苷和黄嘌呤的作用，我们试图通过改变腺苷和黄嘌呤的浓度来改变臭氧所提供的保护作用。缺血后内源性腺苷的代谢消除了臭氧所提供的保护作用。在臭氧处理前给予黄嘌呤时，腺苷所提供的保护作用消失，显示缺血后活性氧和转氨酶水平与肝脏缺血再灌注后相似。臭氧可通过腺苷的蓄积对肝脏缺血再灌注损伤起到保护作用，腺苷进而对肝脏有益，同时通过阻断黄嘌呤/黄嘌呤氧化酶产生活性氧的途径来发挥作用。
