THE STUDY OF INTERACTION HEPATOTOXIC EFFECTS OF BROMO-BENZENE AND THE MARKER ACTIVITY OF THE CYTOCHROME P-450 AND ENZYMES OF CONJUGATION

S.A. Kachula, A.A. Pentiuk, E.V. Tertishna, O.G. Vovk

Bromobenzene when given to a rats per os, a dose of 1 g/kg and when incubated in isolated hepatocytes (0,6 mMoles) causes a major destruction of the liver which is accompanied by excretion of intracellular enzymes, decreased glutathione level and decreased activity, of membrane-bound enzymes. Hepatotoxic effect of bromobenzene is caused to a great extent in hepatocytes with highly active CYP2E1, but on the contrary with highly activities glutathione-S-transferase, UDP-glycuroniltransferase and phenol-sulphotransferase, hepatotoxic effect of bromobenzene is reduced. Preliminary testing of the rats with the help of acetanilide and amidopyrine revealed a strong and direct corelation between the toxicity of bromobenzene and the ability of animals to metabolise acet-anilide up to mercapturic acid, to a small measure with the ability of the rats to oxidize acetanilide up to aminophenolic metabolites, but amidopyrine up to 4-aminoantipyrine. Animals with a very high ability to form glucuronic and sulfatic metabolites of acetanilide proved less sensitive to bromobenzene.

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