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...

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Bibliographic Details
Published in:Toxicology and applied pharmacology 2004-12, Vol.201 (2), p.105-111
Main Authors: Ferioli, Maria Elena, Berselli, Debora, Caimi, Samuela
Format: Article
Language:English
Subjects:
60 APPLIED LIFE SCIENCES
Acetyltransferases - metabolism
Animals
Biogenic Polyamines - metabolism
Biological and medical sciences
BIOSYNTHESIS
CATABOLISM
DECARBOXYLASES
DETOXIFICATION
DNA - biosynthesis
DNA - genetics
DRUGS
ENZYME ACTIVITY
Enzyme Inhibitors - pharmacology
IN VIVO
LIVER
Liver - drug effects
Liver - enzymology
Male
Medical sciences
Mitoguazone
Mitoguazone - toxicity
Oxidoreductases Acting on CH-NH Group Donors - antagonists & inhibitors
Oxidoreductases Acting on CH-NH Group Donors - metabolism
Polyamine Oxidase
Polyamines
PUTRESCINE
RATS
Rats, Wistar
SPERMINE
SUBSTRATES
Toxicology
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Summary: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.
ISSN:0041-008X
1096-0333
DOI:10.1016/j.taap.2004.05.013