Ethanol-associated alterations in the kinetics of putrescine uptake and metabolism by the regenerating liver

A. M. Diehl, Qi Yang Shi Qi Yang, N. Brown, J. Smith, D. Raiford, R. Gordon, Robert A Casero

Research output: Contribution to journalArticle

Abstract

Biosynthesis of the polyamines, putrescine, spermidine, and spermine is required for DNA synthesis and liver regeneration after partial hepatectomy. We have previously reported that chronic ethanol consumption impairs polyamine synthesis and significantly retards liver regeneration after partial hepatectomy. In those studies, supplementation with putrescine restored hepatic DNA synthesis in ethanol-fed rats but exerted no effect in pair-fed controls. These differences in the response to putrescine treatment may have resulted from ethanol-associated differences in hepatic uptake, release, or metabolism of putrescine. To resolve these issues and define more completely how putrescine treatment affects DNA synthesis, we now assess the kinetics of putrescine uptake and metabolism after intraperitoneal or intravenous injection of radiolabeled putrescine (1.2 mmol/kg, specific activity 1 μCi/mmol) into rats fed 36% ethanol diets or isocaloric, nonethanol diets for 6 weeks prior to partial hepatectomy. After putrescine treatment, hepatic putrescine concentrations were greater in ethanol-fed rats than controls. Differences in post-treatment hepatic putrescine levels between ethanol and pair-fed groups could not be explained by differences in the rates of hepatic putrescine uptake or excretion into bile; residual de novo synthesis of putrescine from ornithine or metabolism of hepatic putrescine to its polyamine products, spermidine and spermine. Indeed, supplemental putrescine was not appreciably converted to spermidine or spermine in either ethanol or control rats. Hence, these latter polyamines are unlikely to be responsible for the treatment-associated improvement in DNA synthesis that has been noted in ethanol-fed rats. This suggests that putrescine itself acts to restore hepatic DNA synthesis in ethanol-fed rats.

Original languageEnglish (US)
Pages (from-to)5-10
Number of pages6
JournalAlcoholism: Clinical and Experimental Research
Volume16
Issue number1
StatePublished - 1992

Fingerprint

Enzyme kinetics
Putrescine
Metabolism
Liver
Ethanol
Polyamines
Spermidine
Spermine
Rats
Hepatectomy
Rat control
DNA
Liver Regeneration
Nutrition
Diet
Therapeutics
Ornithine
Biosynthesis
Intraperitoneal Injections
Bile

Keywords

  • Liver Regeneration
  • Ornithine Decarboxylase
  • Polyamines
  • Putrescine

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Toxicology

Cite this

Ethanol-associated alterations in the kinetics of putrescine uptake and metabolism by the regenerating liver. / Diehl, A. M.; Shi Qi Yang, Qi Yang; Brown, N.; Smith, J.; Raiford, D.; Gordon, R.; Casero, Robert A.

In: Alcoholism: Clinical and Experimental Research, Vol. 16, No. 1, 1992, p. 5-10.

Research output: Contribution to journalArticle

Diehl, A. M. ; Shi Qi Yang, Qi Yang ; Brown, N. ; Smith, J. ; Raiford, D. ; Gordon, R. ; Casero, Robert A. / Ethanol-associated alterations in the kinetics of putrescine uptake and metabolism by the regenerating liver. In: Alcoholism: Clinical and Experimental Research. 1992 ; Vol. 16, No. 1. pp. 5-10.
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