S-allylmercaptocysteine scavenges hydroxyl radical and singlet oxygen in vitro and attenuates gentamicin-induced oxidative and nitrosative stress and renal damage in vivo

BMC Clin Pharmacol. 2004 Apr 30:4:5. doi: 10.1186/1472-6904-4-5.

Abstract

Background: Oxidative and nitrosative stress have been involved in gentamicin-induced nephrotoxicity. The purpose of this work was to study the effect of S-allylmercaptocysteine, a garlic derived compound, on gentamicin-induced oxidative and nitrosative stress and nephrotoxicity. In addition, the in vitro reactive oxygen species scavenging properties of S-allylmercaptocysteine were studied.

Results: S-allylmercaptocysteine was able to scavenge hydroxyl radicals and singlet oxygen in vitro. In rats treated with gentamicin (70 mg/Kg body weight, subcutaneously, every 12 h, for 4 days), renal oxidative stress was made evident by the increase in protein carbonyl content and 4-hydroxy-2-nonenal, and the nitrosative stress was made evident by the increase in 3-nitrotyrosine. In addition, gentamicin-induced nephrotoxicity was evident by the: (1) decrease in creatinine clearance and in activity of circulating glutathione peroxidase, and (2) increase in urinary excretion of N-acetyl-beta-D-glucosaminidase, and (3) necrosis of proximal tubular cells. Gentamicin-induced oxidative and nitrosative stress and nephrotoxicity were attenuated by S-allylmercaptocysteine treatment (100 mg/Kg body weight, intragastrically, 24 h before the first dose of gentamicin and 50 mg/Kg body weight, intragastrically, every 12 h, for 4 days along gentamicin-treatment).

Conclusion: In conclusion, S-allylmercaptocysteine is able to scavenge hydroxyl radicals and singlet oxygen in vitro and to ameliorate the gentamicin-induced nephrotoxicity and oxidative and nitrosative stress in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aldehydes / immunology
  • Aldehydes / metabolism
  • Animals
  • Biomarkers / blood
  • Biomarkers / urine
  • Body Weight / physiology
  • Carboxylic Acids / metabolism
  • Cysteine / analogs & derivatives*
  • Cysteine / physiology*
  • Dinitrophenols / immunology
  • Dinitrophenols / metabolism
  • Energy Intake / physiology
  • Free Radical Scavengers / metabolism*
  • Gentamicins / antagonists & inhibitors*
  • Gentamicins / pharmacology*
  • Hydroxyl Radical / metabolism*
  • Immunohistochemistry / methods
  • Kidney Cortex / chemistry
  • Kidney Cortex / enzymology
  • Kidney Cortex / pathology
  • Kidney Diseases / blood
  • Kidney Diseases / etiology*
  • Kidney Diseases / urine
  • Kidney Glomerulus / blood supply
  • Kidney Glomerulus / pathology
  • Kidney Tubules, Proximal / blood supply
  • Kidney Tubules, Proximal / pathology
  • Male
  • Oxidation-Reduction
  • Oxidative Stress / drug effects*
  • Proteins / metabolism
  • Rats
  • Rats, Wistar
  • Reactive Oxygen Species / metabolism*
  • Tyrosine / analogs & derivatives*
  • Tyrosine / immunology
  • Tyrosine / metabolism
  • Urine / physiology

Substances

  • Aldehydes
  • Biomarkers
  • Carboxylic Acids
  • Dinitrophenols
  • Free Radical Scavengers
  • Gentamicins
  • Proteins
  • Reactive Oxygen Species
  • S-allylmercaptocysteine
  • Hydroxyl Radical
  • 3-nitrotyrosine
  • Tyrosine
  • 4-hydroxy-2-nonenal
  • Cysteine