There is increasing evidence that cellular damage in endotoxin induced shock is due at least in part to the generation of free oxygen radicals. Paradoxically, a sublethal dose of endotoxin has also been shown to provide protection against oxidant stress such as myocardial ischemia-reperfusion injury.

To understand the possible role of antioxidant enzyme system in endotoxin induced stress the effect of endotoxin on antioxidant gene expression and antioxidant enzyme activities in homogenates of heart, liver and kidney from Sprague-Dawley rats was compared by quantitation of m-RNA and enzyme activities. Alterations in the message level for Cu-Zn superoxide dismutase(SOD), Mn SOD and catalase varied with the tissue type, length of exposure to endotoxin, and dose of endotoxin. In general, endotoxin treatment reduced Cu-Zn SOD expression in heart and liver, but had no noticeable effect in kidney. Mn SOD message levels were increased in heart and but decreased in liver. Catalase expression was reduced in kidney and increased marginally in heart and liver. With regard to enzyme activity, endotoxin treatment reduced Cu-Zn SOD activity in heart, liver and kidney. Mn SOD activity showed little change in heart, but increased in liver and to a lesser extent in kidney. Catalase activity showed little change in heart and kidney but was decreased in liver 12 hour post-treatment. The differing responses of tissues to the oxidant stress of endotoxin exposure should be considered when evaluating the effect of endotoxin on antioxidant enzymes. (Supported by grants from D.C.I. and N.I.H. NS-22576)