Ischemic preconditioning: a defense mechanism against the reactive oxygen species generated after hepatic ischemia reperfusion.
BACKGROUND
Preconditioning protects against both liver and lung damage after hepatic ischemia-reperfusion (I/R). Xanthine and xanthine oxidase (XOD) may contribute to the development of hepatic I/R.


OBJECTIVE
To evaluate whether preconditioning could modulate the injurious effects of xanthine/XOD on the liver and lung after hepatic I/R.


METHODS
Hepatic I/R or preconditioning previous to I/R was induced in rats. Xanthine and xanthine dehydrogenase/xanthine oxidase (XDH/XOD) in liver and plasma were measured. Hepatic injury and inflammatory response in the lung was evaluated.


RESULTS
Preconditioning reduced xanthine accumulation and conversion of XDH to XOD in liver during sustained ischemia. This could reduce the generation of reactive oxygen species (ROS) from XOD, and therefore, attenuate hepatic I/R injury. Inhibition of XOD prevented postischemic ROS generation and hepatic injury. Administration of xanthine and XOD to preconditioned rats led to hepatic MDA and transaminase levels similar to those found after hepatic I/R. Preconditioning, resulting in low circulating levels of xanthine and XOD activity, reduced neutrophil accumulation, oxidative stress, and microvascular disorders seen in lung after hepatic I/R. Inhibition of XOD attenuated the inflammatory damage in lung after hepatic I/R. Administration of xanthine and XOD abolished the benefits of preconditioning on lung damage.


CONCLUSIONS
Preconditioning, by blocking the xanthine/XOD pathway for ROS generation, would confer protection against the liver and lung injuries induced by hepatic I/R.
Peralta
C
C
Department of Clinical and Biological Sciences, Section Genral Pathology, University of Turin, Italy.
Bulbena
O
O
Xaus
C
C
Prats
N
N
Cutrin
J C
JC
Poli
G
G
Gelpi
E
E
Roselló-Catafau
J
J
D000818:Animals; D005978:Glutathione / Q000378:metabolism; D007511:Ischemia / Q000503:physiopathology* / Q000517:prevention & control; D019194:Ischemic Preconditioning / Q000379:methods*; D008099:Liver / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009504:Neutrophils / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors*; D015424:Reperfusion; D013482:Superoxide Dismutase / Q000378:metabolism; D019820:Xanthine / Q000097:blood / Q000494:pharmacology; D014968:Xanthine Dehydrogenase / Q000494:pharmacology; D014969:Xanthine Oxidase / Q000494:pharmacology
D017382:Reactive Oxygen Species; D019820:Xanthine; D008315:Malondialdehyde; D013482:Superoxide Dismutase; D014968:Xanthine Dehydrogenase; D014969:Xanthine Oxidase; D005978:Glutathione