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 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.
Zanelli
U
U
Istituto di Mutagenesi e Differenziamento, Consiglio Nazionale delle Richerche, Pisa, Italy.
Puccini
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P
Acerbi
D
D
Ventura
P
P
Gervasi
P G
PG
D000818:Animals; D042926:Cytochrome P-450 CYP4A; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis* / Q000502:physiology; D004790:Enzyme Induction / Q000187:drug effects; D007668:Kidney / Q000187:drug effects / Q000201:enzymology*; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D008830:Microbodies / Q000187:drug effects* / Q000201:enzymology*; D006899:Mixed Function Oxygenases / Q000096:biosynthesis* / Q000502:physiology; D010084:Oxidation-Reduction / Q000187:drug effects; D010421:Pentanoic Acids / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014238:Trichloroacetic Acid / Q000494:pharmacology*
D010421:Pentanoic Acids; D014238:Trichloroacetic Acid; C005566:pivalic acid; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; C026961:prostaglandin omega hydroxylases; D042926:Cytochrome P-450 CYP4A