Lead detoxification activity and ADMET hepatotoxicity of N-(alpha-L-arabino-furanos-1-yl)-L-cysteine

Chem Res Toxicol. 2010 Jul 19;23(7):1282-5. doi: 10.1021/tx100155r.

Abstract

N-(alpha-L-Arabinofuranos-1-yl)-L-cysteine was stereoselectively prepared from L-arabinose and l-cysteine. Its in vivo detoxification action was evaluated on lead loaded mice at the doses of 0.1, 0.2, and 0.4 mmol/kg. The results show that lead accumulation in the livers, kidneys, brains, and femurs of the treated mice could be efficiently decreased by N-(alpha-L-arabinofuranos-1-yl)-L-cysteine, even at the dose of 0.1 mmol/kg. Compared with the lead detoxification efficacy, 0.4 mmol/kg of N-(alpha-L-arabinofuranos-1-yl)-L-cysteine did not affect the essential metals in the treated mice, such as Fe, Cu, Zn, and Ca. In the apparent permeability coefficient test, the values of P(app)(A-->B), P(app)(B-->A), and P(app)(A-->B)/P(app)(B-->A) indicated that N-(alpha-L-arabinofuranos-1-yl)-L-cysteine was transported actively across the Caco-2 cell monolayer. Silico molecular modeling results predicted that N-(alpha-L-arabinofuranos-1-yl)-L-cysteine had no hepatotoxicity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arabinose / analogs & derivatives*
  • Arabinose / metabolism
  • Arabinose / pharmacology
  • Arabinose / toxicity
  • Caco-2 Cells
  • Cell Membrane Permeability
  • Cysteine / analogs & derivatives*
  • Cysteine / metabolism
  • Cysteine / pharmacology
  • Cysteine / toxicity
  • Humans
  • Lead / chemistry
  • Lead / metabolism*
  • Lead / toxicity
  • Liver / drug effects
  • Male
  • Mice
  • Stereoisomerism

Substances

  • N-(arabinofuranos-1-yl)cysteine
  • Lead
  • Arabinose
  • Cysteine