BIPHASIC ACTIONS OF CHLORPROMAZINE AND MEPACRINE ON MODULATION OF HEPATIC CELL INJURY IN THE PERFUSED CAT LIVER

  • 1 January 1981
    • journal article
    • research article
    • Vol. 249  (1) , 116-125
Abstract
The effect of chlorpromazine (CPZ) and mepacrine on hypoxic liver cell damage was studied using an isolated perfused cat liver preparation. High concentrations of CPZ (10-4 M) significantly augmented the hypoxic leakage of the lysosomal enzyme, cathepsin D, and the cytoplasmic enzyme, lactate dehydrogenase (LDH) into the perfusate. The percent free cathepsin D activity of hepatic tissue was significantly higher in the 10-4 M CPZ treated group (87%) than in the vehicle group (65%). CPZ at a concentration of 10-6 M possessed a detrimental effect on hypoxic liver integrity but this was less than that at 10-4 M. Low concentrations of CPZ (10-7 M) showed a protective effect during hypoxia (i.e., significantly lower perfusate cathepsin D activity and percent free cathepsin D activity) compared to livers receiving only the vehicle. Mepacrine, another phospholipase A2 inhibitor, showed no significant effect on hypoxic liver damage at concentrations of 10-6 and 5 .times. 10-5 M. CPZ has a biphasic action on liver integrity during hypoxia, low concentrations being protective and high concentrations deleterious. Mepacrine had no significant effect in the hypoxic liver.

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