Protective effect of S-allylcysteine against cyclophosphamide-induced bladder hemorrhagic cystitis in mice

Food Chem Toxicol. 2008 Nov;46(11):3368-74. doi: 10.1016/j.fct.2008.08.011. Epub 2008 Aug 22.

Abstract

S-Allylcysteine (SAC), an organosulfur compound of aged garlic extract (AGE) regulates the thiol status of the cell and scavenges free radicals. Depletion of thiols along with free radical generation has been implicated in cyclophosphamide (CP)-induced urotoxicity. We studied modulatory effect of SAC on CP-induced urotoxicity in mice focusing on hemorrhagic cystitis (HC). SAC (150 and 300 mg kg(-1)) was administered in CP treated animals (200 mg kg(-1)) and bladder was observed for histological and biochemical changes. CP treatment caused a marked increase in the lumen exudates, edema, vasodilation and HC in lamina propia in the bladder. These changes were accompanied by increase in lipid peroxidation (LPO), and decrease in reduced glutathione (GSH) and activities of antioxidant enzymes. SAC not only showed protection in tissue histology but also improved the decreased activities of antioxidant enzymes. SAC treatment also reduced LPO and increased GSH levels. Although SAC treatment did not ensure full recovery, the marked improvement in histology and antioxidants of bladder suggests that it has a significant modulatory effect on CP-induced urotoxicity. Since decrease in antioxidant level is the major cause of CP urotoxicity, the protective effect of SAC deserves its further exploration involving laboratory and clinical investigations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents, Alkylating / toxicity
  • Antioxidants / metabolism
  • Cyclophosphamide / toxicity*
  • Cysteine / analogs & derivatives*
  • Cysteine / pharmacology
  • Cystitis / chemically induced*
  • Cystitis / metabolism
  • Cystitis / pathology
  • Cystitis / prevention & control*
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Free Radical Scavengers / metabolism
  • Free Radicals / metabolism
  • Glutathione / metabolism
  • Lipid Peroxidation / drug effects
  • Male
  • Mice
  • Oxidation-Reduction
  • Random Allocation
  • Urinary Bladder / drug effects*
  • Urinary Bladder / metabolism
  • Urinary Bladder / pathology*

Substances

  • Antineoplastic Agents
  • Antineoplastic Agents, Alkylating
  • Antioxidants
  • Free Radical Scavengers
  • Free Radicals
  • S-allylcysteine
  • Cyclophosphamide
  • Glutathione
  • Cysteine