Effect of “Drugs for Liver Disease” on Hepatotoxic Action of Carbon Tetrachloride: I. Changes of Lysosomal Enzyme Levels and Effect of Protoporphyrin on the Levels

Abstract

In order to clarify the action of drugs for liver disease, the effect of protoporphyrin (PP) on CCl4-induced liver injury was studied. Attention was given to the levels of lysosomal enzymes, some components of the liver, and inhibition of enzymes and lysis of lysosomal membranes by lipid peroxides. Administration of PP to CCl4-poisoned rats was found to prevent the decrease in lysosomal lipolytic enzyme level in the liver, but not in other enzyme levels tested. The inhibition of lipolytic enzyme by CCI, administered may be partially involved in lipid accumulation in the liver. A dose of PP administered to CCl4-poisoned rats for 8 days depressed the neutral lipid content in the liver nearly to the control value. Methyl linoleate hydroperoxide (hydroperoxide) at a lower concentration of 10−6% inhibited the lipolytic enzyme activity by 30% and in concentrations ranging from 10−4 to 10−3% inhibited β-glucuronidase activity. Addition of PP to the medium containing 10−6 to 10−5% hydroperoxide and α-tocophcrol reduced the enzyme inhibition further than in the absence of PP. The hydroperoxide in concentrations varying from 10−6 to 10−3% caused a partial lysis of liver lysosomal membranes, but addition of PP slightly reduced the damage by the hydroperoxide in concentrations lower than 10−5%.