Induction of peroxisomal beta-oxidation and P-450 4A-dependent activities by pivalic and trichloroacetic acid in rat liver and kidney

• Published in: Archives of toxicology Vol. 70; no. 3-4; p. 145
• Main Authors: Zanelli, U, Puccini, P, Acerbi, D, Ventura, P, Gervasi, P G
• Format: Journal Article
• Language: English
• Published: Germany 1996
• Subjects: Animals; Cytochrome P-450 CYP4A; Cytochrome P-450 Enzyme System - biosynthesis; Cytochrome P-450 Enzyme System - physiology; Enzyme Induction - drug effects; Kidney - drug effects; Kidney - enzymology; Liver - drug effects; Liver - enzymology; Male; Microbodies - drug effects; Microbodies - enzymology; Mixed Function Oxygenases - biosynthesis; Mixed Function Oxygenases - physiology; Oxidation-Reduction - drug effects; Pentanoic Acids - pharmacology; Rats; Rats, Sprague-Dawley; Trichloroacetic Acid - pharmacology
• ISSN: 0340-5761
• DOI: 10.1007/s002040050253

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 resulted in a similar and selective induction (2-3 times) of peroxisomal palmitoyl-CoA oxidase and the cytochrome P-450 4A dependent microsomal (omega)- and (omega-1)-lauric acid activities, both in liver and kidney. Western blot analysis of liver and kidney microsomes from PIV- and TCA-treated rats, using antibody to the P-450 4A1, revealed induction of members of the P-450 4A subfamily. These results suggest that PIV, like TCA, is a renal and hepatic peroxisome proliferator in rats, and further support the previously indicated close association between the peroxisomal fatty acid beta-oxidation enzymes and microsomal P-450 4A sub-family enzymes.