Preconditioning protects liver and lung damage in rat liver transplantation: role of xanthine/xanthine oxidase.
This study was designed to evaluate whether ischemic preconditioning could confer protection against liver and lung damage associated with liver transplantation. The effect of preconditioning on the xanthine/xanthine oxidase (XOD) system in liver grafts subjected to 8 and 16 hours of cold ischemia was also evaluated. Increased xanthine levels and marked conversion of xanthine dehydrogenase (XDH) to XOD were observed after hepatic cold ischemia. Xanthine/XOD could play a role in the liver and lung damage associated with liver transplantation. This assumption is based on the observation that inhibition of XOD reduced postischemic reactive oxygen species (ROS) generation and hepatic injury as well as ensuing lung inflammatory damage, including neutrophil accumulation, oxidative stress, and edema formation. Ischemic preconditioning reduced xanthine accumulation and conversion of XDH to XOD in liver grafts during cold ischemia. This could diminish liver and lung damage following liver transplantation. In the liver, preconditioning prevented postischemic ROS generation and hepatic injury as well as the injurious effects in the lung following liver transplantation. Administration of xanthine and XOD to preconditioned rats led to hepatic ROS and transaminase levels similar to those found after reperfusion and abolished the protective effect of preconditioning on the lung inflammatory damage. In conclusion, ischemic preconditioning reduces both liver and lung damage following liver transplantation. This endogenous protective mechanism is capable of blocking xanthine/XOD generation in liver grafts during cold ischemia.
Department of Experimental Pathology, Instituto de Investigaciones Biomédicas de Barcelona-Consejo Superior de Investigaciones Científicas, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain.
Leticia
L
Fernández
Nicolás
N
Heredia
Luis
L
Grande
Gloria
G
Gómez
Antonio
A
Rimola
Alberto
A
Marco
Emilio
E
Gelpí
Joan
J
Roselló-Catafau
Carmen
C
Peralta
D000818:Animals; D003080:Cold Temperature; D007511:Ischemia / Q000378:metabolism / Q000473:pathology; D019194:Ischemic Preconditioning; D008099:Liver / Q000201:enzymology* / Q000473:pathology; D016031:Liver Transplantation; D008168:Lung / Q000201:enzymology* / Q000473:pathology; D008297:Male; D019188:Organ Preservation Solutions; D011654:Pulmonary Edema / Q000201:enzymology / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D014969:Xanthine Oxidase / Q000378:metabolism*; D014970:Xanthines / Q000378:metabolism
D019188:Organ Preservation Solutions; D017382:Reactive Oxygen Species; D014970:Xanthines; D014969:Xanthine Oxidase