INDUCTION OF PEROXISOMAL BETA-OXIDATION AND P-450 4A-DEPENDENT ACTIVITIES BY PIVALIC AND TRICHLOROACETIC-ACID IN RAT-LIVER AND KIDNEY

The influence of pivalic acid (PIV), a compound often used to make pro -drugs, and of the structurally related trichloroacetic acid (TCA), on several hepatic and renal enzymes was investigated in Sprague-Dawley rats, following a 4-day treatment period. The PIV and TCA treatments r esulted in a similar and selective induction (2-3 times) of peroxisoma l palmitoyl-CoA oxidase and the cytochrome P-450 4A dependent microsom al (omega)- and (omega-1)-lauric acid activities, both in liver and ki dney. Western blot analysis of liver and kidney microsomes from PIV- a nd TCA-treated rats, using antibody to the P-450 4A1, revealed inducti on of members of the P-450 4A subfamily. These results suggest that PI V, like TCA, is a renal and hepatic peroxisome proliferator in rats, a nd further support the previously indicated close association between the peroxisomal fatty acid beta-oxidation enzymes and microsomal P-450 4A sub-family enzymes.