Physiological responses to endotoxin in copper deficient rats

Abstract

Copper deficient rats show high mortality after a normally sublethal dose of endotoxin. To begin examining the mechanisms, this study examined copper deficiency effects on certain responses to endotoxin. Weanling rats were fed 0.2 or 8 ppm copper for 5 weeks; endotoxin was given at 10 mg/kg, ip. Copper deficiency was confirmed by low activities of ceruloplasmin, and liver and serum superoxide dismutase. Compared to adequate rats, deficients showed the following responses to endotoxin: elevated serum transaminase activities (an indication of liver injury), prolonged hyperglycemia, slightly enhanced liver glycogen depletion, high resistance to hepatic lysosomel enzyme leakage, normal degree of rapid onset hypotension, no microvascular injury based on albumin clearance, slightly higher acute phase response based on serum zinc, and normal increase of tumor necrosis factor at typical time of peak accumulation. Thus, endotoxin-induced mortality in copper deficient rats may derive, at least in part, from a selective liver injury, but not from excessive serum glucose or liver glycogen depletion, impaired acute phase response, aggravated short term hypotension, exaggerated tumor necrosis factor release, fragile lysosomes or excessive microvascular injury.