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| Nitrite-derived nitric oxide by xanthine oxidoreductase protects the liver against ischemia-reperfusion injury |
| Ping Lü, Fang Liu, Zhong Yao, Chun-You Wang, Dao-Da Chen, Yuan Tian, Jing-Hui Zhang and Yi-Hua Wu |
Wuhan, China
Author Affiliations: Department of General Surgery (Lü P, Wang CY and Chen DD), and Department of Radiology(Liu F), Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Cold Spring Harbor Laboratory, New York 11724, USA (Yao Z); General Surgery Laboratory, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China (Tian Y, Zhang JH and Wu YH)
Corresponding Author: Ping Lü, MD, Department of General Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China (Tel: 86-27-85726273; Fax: 86-27-85726830; Email: luliu@public.wh.hb.cn) |
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Abstract BACKGROUND: It was demonstrated that xanthine oxidoreductase (XOR), during ischemia, catalyzes the formation of nitric oxide (NO) from nitrite (NO2-) and this NO2--derived NO protects the isolated perfused rat heart against thedamaging effects of ischemia-reperfusion (I/R) when conventional nitric oxide synthase (NOS)-dependent NO production is impaired. Liver is one of the organs with the highest XOR concentration. This study was designed to determine whether NO2--derived NO by XOR protects liver against I/R injury in vivo. For its minute amounts and active reactivity, NO cannot be detected directly in real time in vivo by this time. We have to prove the above hypothesis indirectly.
METHODS: Wistar rats were pretreated with saline, NOS inhibitor L-NAME (10 mg/kg intravenously), XOR inhibitor allopurinol (1.5 mg/kg orally), L-NAME+allopurinol and NO scavenger carboxy-PTIO (0.6 mg/kg intravenously) respectively (12 animals per group). And then, they were subjected to total liver ischemia for 40 minutes followed by reperfusion. Blood samples and liver tissues were obtained for analysis after 3 hours of reperfusion. Survival was also investigated.
RESULTS: Allopurinol-treated animals exhibited further increased serum alanine aminotransferase(ALT) levels and liver myeloperoxidase(MPO) activities, but further decreased liver adenosine triphosphate (ATP) stores after I/R compared to saline-treated counterparts (830.5±108.3 U/L, 56.5±11.0U/mg protein and 1.93±0.47μmol/g vs. 505.8±184.2 U/L, 41.5±10.2 U/mg protein and 3.05±0.55μmol/g respectively, P＜0.01, P＜0.05 and P＜0.01 respectively). The hepatocyte injury was further exacerbated and the overall survival rate was significantly decreased after I/R in animals given by allopurinol compared to those pretreated by saline (P＜0.05). L-NAME and allopurinol co-treated animals exhibited more severe liver injury (P＜0.05 and P＜0.01) and a further decreased overall survival rate (P＜0.05)compared to L-NAME or allopurinol alone-treated counterparts, but they were not different from carboxy-PTIO treated animals (P>0.05).
CONCLUSION: NO2--derived NO by XOR in the hypoxic and acidic environment induced by hepatic I/R protects the liver against I/R injury in vivo.
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2005, Vol. 4 
