Alleviation of carrageenan-induced hepatotoxicity and acronecrosis by aprotinin

Carrageenan was found to be hepatotoxic in mice. Raised serum transaminase activity after i.p. injection of carrageenan was correlated with histopathological changes in the liver. These included necrosis of individual hepatocytes and focal areas of necrosis, with associated fibrin thrombi, 12 h after carrageenan injection. Increased mitotic activity was observed at 72 h and extramedullary haemopoiesis was noted at Day 5. Acronecrosis, a further manifestation of intravascular coagulation, was evident within 24 h of carrageenan injection, becoming clearly demarcated by Day 5. Treatment with the anti-protease aprotinin alleviated both the hepatotoxicity and the incidence and extent of acronecrosis induced by carrageenan. The possible mechanism underlying the in vivo toxicity of carrageenan and its alleviation by aprotinin is discussed in the light of these and other findings.