Tempol, an intracelullar free radical scavenger, reduces liver injury in hepatic ischemia-reperfusion in the rat

被引:37
作者
Sepodes, B
Maio, R
Pinto, R
Marques, C
Mendes-Do-Vale, J
McDonald, MC
Thiemermann, C
Mota-Filipe, H
机构
[1] Univ Lisbon, Fac Farm, Unidade Farmacol & Farmacotoxicol, P-1649019 Lisbon, Portugal
[2] Univ Lisbon, Sch Pharm, P-1649019 Lisbon, Portugal
[3] Hosp Santa Maria, Transplantat Surg Unit 3, Lisbon, Portugal
[4] St Bartholomews & Royal London Sch Med & Dent, William Harvey Res Inst, London, England
关键词
D O I
10.1016/j.transproceed.2004.03.050
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Liver ischemia is of clinical interest because of its role in liver failure and also hepatic graft rejection. The generation of reactive oxygen species contributes to the injury that follows ischemia-reperfusion. One therapy utilizes the administration of antioxidants; however, only limited experience suggests a potential benefit of systemic administration of these compounds. To overcome the limitations of these compounds, small molecules with improved cell membrane permeability characteristics and higher potency, such as tempol, are being tested in vivo. Tempol, a membrane-permeable radical scavenger, interferes with the formation or the effects of many radicals, including superoxide anions, hydroxyl radicals, and peroxynitrite. The aim of this study was to investigate the effects of tempol in an in vivo rat model of liver ischemia-reperfusion injury. Male Wistar rats were pretreated with tempol (30 mg/kg, IV) 5 minutes prior to liver ischemia (for 30 minutes) and reperfusion (for 2 hours). The liver injury was assessed by measuring serum levels of transaminases, lactate dehydrogenase, and gamma-glutamyl transferase. Tempol significantly mitigated the increase in transaminases, lactate dehydrogenase, and gamma-glutamyl transferase following liver ischemia-reperfusion, suggesting an improvement in liver function and resistance to injury.
引用
收藏
页码:849 / 853
页数:5
相关论文
共 24 条
[21]   Up-regulation of oxygen-derived free radicals by interleukin-1 in hepatic ischemia/reperfusion injury. [J].
Shirasugi, N ;
Wakabayashi, G ;
Shimazu, M ;
Oshima, A ;
Shito, M ;
Kawachi, S ;
Karahashi, T ;
Kumamoto, Y ;
Yoshida, M ;
Kitajima, M .
TRANSPLANTATION, 1997, 64 (10) :1398-1403
[22]   Redox regulation of transcriptional activators [J].
Sun, Y ;
Oberley, LW .
FREE RADICAL BIOLOGY AND MEDICINE, 1996, 21 (03) :335-348
[23]   Membrane-permeable radical scavengers (tempol) for shock, ischemia-reperfusion injury, and inflammation [J].
Thiemermann, C .
CRITICAL CARE MEDICINE, 2003, 31 (01) :S76-S84
[24]   DIRECT MEASUREMENT OF FREE-RADICAL GENERATION FOLLOWING REPERFUSION OF ISCHEMIC MYOCARDIUM [J].
ZWEIER, JL ;
FLAHERTY, JT ;
WEISFELDT, ML .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1987, 84 (05) :1404-1407