PHYSIOLOGICAL-RESPONSES TO ENDOTOXIN IN COPPER-DEFICIENT RATS

Copper deficient rats show high mortality after a normally sublethal d ose of endotoxin. To begin examining the mechanisms, this study examin ed copper deficiency effects on certain responses to endotoxin. Weanli ng 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 a dequate 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 lysosomal enzyme leakage, normal degree of rapid onset hypotension, no microvascular injury based on albumin cle arance, slightly higher acute phase response based on serum zinc, and normal increase of tumor necrosis factor at typical time of peak accum ulation. Thus, endotoxin-induced mortality in copper deficient rats ma y derive, at least in part, from a selective liver injury, but not fro m excessive serum glucose or liver glycogen depletion, impaired acute phase response, aggravated short term hypotension, exaggerated tumor n ecrosis factor release, fragile lysosomes or excessive microvascular i njury.