Effect of mitoguazone on polyamine oxidase activity in rat liver

• Published in: Toxicology and applied pharmacology Vol. 201; no. 2; pp. 105 - 111
• Main Authors: Ferioli, Maria Elena, Berselli, Debora, Caimi, Samuela
• Format: Journal Article
• Language: English
• Published: San Diego, CA Elsevier Inc 01.12.2004; Elsevier
• 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; Rats; Polyamine oxidase; Polyamines; Liver; Mitoguazone; Antineoplastic agent; Rat; Digestive system; Enzyme; Rodentia; Activity; Polyamines: Rats; Vertebrata; Mammalia; Animal; Oxidoreductases
• ISSN: 0041-008X; 1096-0333
• DOI: 10.1016/j.taap.2004.05.013

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.