Effect of mitoguazone on polyamine oxidase activity in rat liver.
Mitoguazone is a known inhibitor of polyamine biosynthesis through competitive inhibition of S-adenosylmethionine decarboxylase. A recent renewed interest in mitoguazone as an antineoplastic agent prompted us to investigate the effect of the drug on polyamine catabolism in rat liver, since the organ plays an important role in detoxification mechanisms. Thus, the purpose of this work was to evaluate the effect of in vivo mitoguazone administration on polyamine catabolic enzymes. In particular, our interest was directed to the changes in polyamine oxidase activity, since this enzyme has been recently confirmed to exert important functions that until now were underestimated. Mitoguazone administration induced hepatic polyamine oxidase activity starting at 4 h after administration, and the enzyme returned to basal levels 96 h after treatment. The changes in enzyme activity were accompanied by changes in putrescine concentrations, which increased starting at 4 h until 72 h after treatment. We also evaluated the activity of the newly identified spermine oxidase, which was not significantly changed by mitoguazone treatment. Therefore, we hypothesized that the enzyme involved in mitoguazone response of the liver is the polyamine oxidase, which acts on acetylated polyamines as substrate.
Ferioli
Maria Elena
ME
ITB-C.N.R. and Institute of General Pathology, University of Milan, Generale, Milan 20133, Italy. MariaElena.Ferioli@unimi.it
Berselli
Debora
D
Caimi
Samuela
S
D000123:Acetyltransferases / Q000378:metabolism; D000818:Animals; D015317:Biogenic Polyamines / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis / Q000235:genetics; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D008935:Mitoguazone / Q000633:toxicity*; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D000097667:Polyamine Oxidase; D000099228:Diamine N-Acetyltransferase
D000123:Acetyltransferases; D015317:Biogenic Polyamines; D004247:DNA; D004791:Enzyme Inhibitors; D008935:Mitoguazone; D000587:Oxidoreductases Acting on CH-NH Group Donors; D000097667:Polyamine Oxidase; D000099228:Diamine N-Acetyltransferase