Hyperthermic liver perfusion and release of lysosomal enzymes

Perfused rat liver was used to study the relationship between the hepatotoxic effects of hyperthermia and the effects of heat on lysosomes. Livers from fed rats were perfused for 180 min at 37-43 degrees C. Release of lysosomal enzymes into the perfusate during perfusion and lysosomal fragility at the end of perfusion were determined. Lysosomes were then incubated in vitro at 37-45 degrees C with xanthine and xanthine oxidase to generate superoxide in order to study lipid peroxidation as a potential causative factor in heat-induced lysosomal lability. Perfusate lysosomal enzymes p-nitrophenyl phosphatase and beta-glucuronidase increased significantly (P less than 0.05) at 42 and 43 degrees C over enzyme levels at 37 degrees C. Significant differences were not observed until after 120 min. Lysosomal fragility was found to be significantly increased (P less than 0.05) after perfusion at 42 and 43 degrees C when measuring p-nitrophenyl phosphatase, but not when measuring beta-glucuronidase activity. Xanthine oxidase acting on xanthine caused labilization of the lysosomes at all temperatures studied when compared to a control at each temperature. There was a temperature effect with an increase in release of p-nitrophenyl phosphatase and beta-glucuronidase from control lysosomes which became significant (P less than 0.05) at 43 degrees C on comparison to 37 degrees C. There were no significant increases in lysosomal lability with temperature in the presence of xanthine and xanthine oxidase. Lastly, salicylic acid peroxidation was used as a measure of superoxide formation from the action of xanthine oxidase with increasing temperature.(ABSTRACT TRUNCATED AT 250 WORDS)