Effect of acetone administration on renal, pulmonary and hepatic monooxygenase activities in hamster.
Administration of acetone in drinking water to Syrian Golden hamsters for 9-10 days altered microsomal P-450 dependent monooxygenase activities in the liver and the kidney but not in the lung. While hepatic microsomal NADPH-cytochrome c reductase was unaffected, cytochrome b5 and P-450 content increased (about 100%) in liver but not in kidney. Furthermore acetone treatment resulted in an increase of microsomal reverse type I binding with DMSO and in an increase in the P-450IIE1-linked renal and hepatic activities such as aniline hydroxylase (AnH) and p-nitrophenol hydroxylase (pNPH). The SDS-PAGE analysis confirmed the induction in acetone-treated microsomes of a hepatic protein with the M.W. of ethanol inducible P-450IIE1 of hamster. The acetone treatment however, unlike ethanol, induced other activities such as benzphetamine N-demethylase and ethoxycoumarin O-deethylase in liver and aminopyrine N-demethylase in kidney. No change of ethoxyresorufin O-deethylase and pentoxyresorufin O-depentylase was observed in either renal or hepatic microsomes. Addition of acetone in vitro had an inhibitory effect on pNPH by hepatic microsomes from control or acetone induced hamsters, while AnH was not affected. Interruption of acetone administration for 24 h resulted in a return of AnH and pNPH activities to essentially basal levels in the liver suggesting a rapid turnover of the hamster P-450IIE1 (ham P-450j). Our results indicate that, as found in rat, acetone is a good inducer of the P-450IIE1 (ham P-450j) in hamster in both the liver and kidney. However other P-450 forms, such as, probably, the renal and hepatic P-450IIB1, are also induced. Thus acetone-treated hamsters, which, in certain respects, show a qualitatively different induction pattern from that reported for ethanol, can be used as an useful animal model to study the toxicity of certain xenobiotics.
Menicagli
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Istituto di Mutagenesi e Differenziamento, Consiglio Nazionale delle Ricerche, Pisa, Italy.
Puccini
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Longo
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Gervasi
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D000096:Acetone / Q000494:pharmacology*; D000284:Administration, Oral; D000818:Animals; D006224:Cricetinae; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004121:Dimethyl Sulfoxide / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D004789:Enzyme Activation / Q000187:drug effects; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008168:Lung / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D008647:Mesocricetus; D008861:Microsomes / Q000187:drug effects / Q000201:enzymology; D010105:Oxygenases / Q000378:metabolism*
D000096:Acetone; D003577:Cytochrome P-450 Enzyme System; D010105:Oxygenases; D004121:Dimethyl Sulfoxide