Effects of new antioxidant compounds PNU-104067F and PNU-74389G on antioxidant defense in normal and diabetic rats

Frederick M. Rauscher, Ruth A. Sanders, John B. Watkins

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Diabetes mellitus and its complications are associated with elevated oxidative stress, leading to much interest in antioxidant compounds as possible therapeutic agents. Two new classes of antioxidant compounds, the pyrrolopyrimidines and the 21-aminosteroids, are known to inhibit lipid peroxidation and other biomolecular oxidation. We hypothesized that in the presence of excess oxidants or the impaired antioxidant defense seen in diabetes mellitus, administration of antioxidants such as these may reverse the effects of diabetes on antioxidant parameters. This study measured the effects of subchronic (14 day) treatment with a pyrrolopyrimidine (PNU-104067F) or a 21-aminosteroid (PNU-74389G) in normal and diabetic Sprague-Dawley rats. Activity levels of Superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase, concentrations of oxidized and reduced glutathione, and lipid peroxidation were used as measures of antioxidant defense in liver, kidney, heart, and brain tissue. In normal rats, the only effect was a 43% increase in cardiac lipid peroxidation after treatment with PNU-104067E In diabetic rats, the only reversals of the effects of diabetes were a 30% decrease in hepatic glutathione peroxidase activity after PNU-74389G treatment and a 33% increase in cardiac glutathione disulfide concentration after PNU-104067F treatment. In contrast to these effects, increased cardiac glutathione peroxidase and catalase activities, increased brain glutathione peroxidase activity, increased hepatic lipid peroxidation, decreased hepatic glutathione content, and decreased hepatic catalase activity were seen in diabetic rats, reflecting an exacerbation of the effects of diabetes.

Original languageEnglish
Pages (from-to)189-194
Number of pages6
JournalJournal of Biochemical and Molecular Toxicology
Volume14
Issue number4
StatePublished - 2000

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Rats
Medical problems
Antioxidants
Glutathione Peroxidase
Lipid Peroxidation
Liver
Catalase
Lipids
Glutathione Disulfide
Glutathione
Brain
Oxidative stress
Glutathione Reductase
Diabetes Complications
Oxidants
Superoxide Dismutase
Sprague Dawley Rats
PNU 104067F
Diabetes Mellitus
Oxidative Stress

Keywords

  • 21-Aminosteroid
  • Brain
  • Diabetes
  • Heart
  • Kidney
  • Liver
  • Oxidative stress
  • Pyrrolopyrimidine

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Health, Toxicology and Mutagenesis
  • Toxicology

Cite this

Effects of new antioxidant compounds PNU-104067F and PNU-74389G on antioxidant defense in normal and diabetic rats. / Rauscher, Frederick M.; Sanders, Ruth A.; Watkins, John B.

In: Journal of Biochemical and Molecular Toxicology, Vol. 14, No. 4, 2000, p. 189-194.

Research output: Contribution to journalArticle

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