Induction of peroxisomal β-oxidation and P-450 4A-dependent activities by pivalic and trichloroacetic acid in rat liver and kidney |
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| Authors: | U. Zanelli P. Puccini D. Acerbi P. Ventura P. G. Gervasi |
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| Affiliation: | (1) Laboratory of Genetic and Biochemical Toxicology, Istituto di Mutagenesi e Differenziamento, Consiglio Nazionale delle Ricerche, via Svezia 10, I-56124 Pisa, Italy, IT;(2) Chiesi Farmaceutici spa via Palermo 26/A I-43100 Parma, Italy, IT |
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| Abstract: | 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 (ω)- and (ω-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 β-oxidation enzymes and microsomal P-450 4A subfamily enzymes. Received: 7 February 1995 / Accepted: 21 August 1995 |
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| Keywords: | P-450 4A induction Palmitoyl-CoA oxidase induction Pivalic acid Trichloroacetic acid |
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