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Tytuł oryginału: Superoxide dismutase mimetic with catalase activity, EUK-134, attenuates the multiple organ injury and dysfunction caused by endotoxin in the rat.
Autorzy: Villa Bianca Roberta d'Emanuele di, Wayman Nicol S., McDonald Michelle C., Pinto Aldo, Sharpe Martyn A., Chatterjee Prabal K., Thiemermann Christoph
Źródło: Med. Sci. Monitor 2002: 8 (1) s.BR1-BR7, il., tab., bibliogr. 33 poz.
Sygnatura GBL: 313,278

Hasła klasyfikacyjne GBL:
  • farmacja
  • traumatologia i ortopedia

    Typ dokumentu:
  • praca doświadczalna
  • tytuł obcojęzyczny

    Wskaźnik treści:
  • zwierzęta
  • szczury

    Streszczenie angielskie: Reactive oxygen species contribute to the multiple organ failure shock. Here we investigate the effects of a salen-manganese complex, which exhibits both superoxide dismutase and catalase activity (EUK-134), on the circulatory failure and the renal and liver injury and dysfunction caused by endotoxin in the anaesthetised (thiopentone, 120 mg/kg) rat. Male Wistar rats were anaesthetised with hiopentone sodium (120 kg i.p.) and instrumented for the measurements of systemic haemodynamics. Animals received lipopolysaccharide (LPS, E. coli, 6 mg/kg i.v.) or saline and were treated with either EUK-134 (0.3 or 1 mg/kg bolus injection folloowed by an infusion of 0.3 or 1 mg/kg/h) or its vehicle (saline). After 6 h of endotoxaemia, blood was taken to evaluate biochemical parameters of organ injury and dysfunction. All data are mean ń s.e. mean of n observations. Statisstical comparisons were made with a ANOVA followed by Dunner's test for mulitiple comparisons. Endotoxaemia for 6 h caused hypotension, renal dysfunction, liver injury, skeletal-muscle injury and pancreatic injury. Treatment of rats with EUK-134 attenuated the reanl dysfynction as well as the liver and skeletal muscle injury (but not the pancreatic injury) caused by endotoxin. Thus, an enhanced formation of reactive oxygen species importantly contribute to the organ injury and dysfunction associated wtih endotoxic shock. We propose that small molecules, which have the catalytic activity of both superoxide dismutase and catalase, may represent a novel therapeutic approach for the therapy of endotoxic shock.

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