Antioxidant activity and low toxicity of (E)-1-(1-(methylthio)-1-(selenopheny) hept-1-en-2-yl) pyrrolidin-2-one

Cell Biol Toxicol. 2012 Aug;28(4):213-23. doi: 10.1007/s10565-012-9217-y. Epub 2012 Mar 13.

Abstract

The aim of the present study was to evaluate the potential pharmacological and toxicological properties of (E)-1-(1-(methylthio)-1-(selenopheny) hept-1-en-2-yl) pyrrolidin-2-one (compound 1), an organoselenium compound. In vitro experiments showed that compound 1 presented a reduction in the lipid peroxidation induced by Fe²⁺ in thiobarbituric acid-reactive species (TBARS) production, and in the generation of reactive species caused by Fe²⁺/malonate in DCFH-DA oxidation. The high dose (500 mg/kg) induced an increase on ALT but not on AST activity. Hepatic, but not cerebral, δ-ALA-D activity from mice treated with 500 mg/kg presented a significant inhibition. Brain catalase activity was significantly inhibited by 100 mg/kg whereas hepatic catalase activity showed a significant increase at all doses. Hepatic lipid peroxidation was diminished only at lowest dose (100 mg/kg) whereas for brain tissue, all doses induced a significant reduction in TBARS levels. Brain and liver ascorbic acid contents were increased only at highest dose of compound 1. Urea and creatinine levels were not significantly altered by treatments. This is a promising compound with antioxidant activity and low toxicity, suggesting the potential beneficial activity of compound 1 against oxidative damage in many parameters studied in rats and mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alanine Transaminase / blood
  • Analysis of Variance
  • Animals
  • Antioxidants / pharmacology*
  • Antioxidants / toxicity
  • Ascorbic Acid / metabolism
  • Aspartate Aminotransferases / blood
  • Brain / drug effects
  • Brain / enzymology
  • Catalase / metabolism
  • Creatinine / blood
  • Ferrous Compounds / pharmacology
  • Lipid Peroxidation / drug effects
  • Liver / drug effects
  • Liver / enzymology
  • Male
  • Mice
  • Organoselenium Compounds / pharmacology*
  • Organoselenium Compounds / toxicity
  • Oxidants / pharmacology
  • Porphobilinogen Synthase / metabolism
  • Rats
  • Rats, Wistar
  • Reactive Oxygen Species / metabolism
  • Thiobarbituric Acid Reactive Substances / metabolism
  • Tissue Extracts
  • Urea / blood

Substances

  • (E)-1-(1-(methylthio)-1-(selenophenyl)hept-1-en-2-yl)pyrrolidin-2-one
  • Antioxidants
  • Ferrous Compounds
  • Organoselenium Compounds
  • Oxidants
  • Reactive Oxygen Species
  • Thiobarbituric Acid Reactive Substances
  • Tissue Extracts
  • Urea
  • Creatinine
  • Catalase
  • Aspartate Aminotransferases
  • Alanine Transaminase
  • Porphobilinogen Synthase
  • Ascorbic Acid