title: Prophylactic efficacy of S-2(2-aminoethylamino)ethyl phenyl sulfide (DRDE-07) against sulfur mustard induced lung toxicity in mice.
abstract: OBJECTIVE
  The present study was planned to investigate the prophylactic efficacy of S-2(2-aminoethylamino)ethyl phenyl sulfide (DRDE-07), against topically applied SM induced pulmonary toxicity in mouse.
  
  
  METHODS
  Animals were pretreated with S-2(2-aminoethylamino)ethyl phenyl sulfide (DRDE-07) (249.4 mg/kg by oral gavage) 30 minutes before SM exposure. The SM (6.48 mg/kg) was applied on hair clipped dorsocaudal region (percutaneous) of the animal. The animals were sacrificed on day 1, 3, 5 and 7. The biochemical changes those were observed in the bronchoalveolar lavage (BAL) fluid and lung tissue included protein, LDH, MPO, β-glucuronidase, MMP-2, MMP-9, activated macrophages, reduced glutathione and lipid peroxidation level.
  
  
  CONCLUSIONS
  Pretreatment with DRDE-07 (0.2 LD50) attenuated SM-induced changes at all time point tested. BAL fluid biochemical endpoints indicated epithelial and endothelial cell damages as evidenced by increase in BAL protein, LDH level and increased number of activated macrophages. The increased myeloperoxidase activity and β-glucuronidase level exhibited the degranulation of neutrophils due to SM toxicity in lung. The zymogrphy analysis of BAL fluid showed a significant increase in matrix metalloproteases (MMP) activity due to inflammatory cells accumulation.
  
  
  CONCLUSIONS
  Thirty minutes pretreatment with DRDE-07 decreased vascular permeability reduced the inflammation and oxidative stress, hence may be recommended as a potential prophylactic agent for SM intoxication.
authors.affiliation: a Division of Pharmacology and Toxicology and.
authors.forename: G M
authors.initials: GM
authors.lastname: Kannan
authors.affiliation: a Division of Pharmacology and Toxicology and.
authors.forename: Pravin
authors.initials: P
authors.lastname: Kumar
authors.affiliation: a Division of Pharmacology and Toxicology and.
authors.forename: A S B
authors.initials: AS
authors.lastname: Bhaskar
authors.affiliation: b Division of Synthetic Chemistry, Defence Research and Development Establishment , Gwalior , Madhya Pradesh , India.
authors.forename: U
authors.initials: U
authors.lastname: Pathak
authors.affiliation: a Division of Pharmacology and Toxicology and.
authors.forename: Deo
authors.initials: D
authors.lastname: Kumar
authors.affiliation: a Division of Pharmacology and Toxicology and.
authors.forename: D P
authors.initials: DP
authors.lastname: Nagar
authors.affiliation: a Division of Pharmacology and Toxicology and.
authors.forename: S C
authors.initials: SC
authors.lastname: Pant
authors.affiliation: b Division of Synthetic Chemistry, Defence Research and Development Establishment , Gwalior , Madhya Pradesh , India.
authors.forename: K
authors.initials: K
authors.lastname: Ganesan
mesh_terms: D000279:Administration, Cutaneous; D000284:Administration, Oral; D004999:Amifostine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D002619:Chemical Warfare Agents / Q000633:toxicity*; D005260:Female; D005434:Flow Cytometry; D005966:Glucuronidase / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D055370:Lung Injury / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D008262:Macrophage Activation / Q000187:drug effects; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000276:immunology; D051379:Mice; D009151:Mustard Gas / Q000633:toxicity*; D020556:Neutrophil Infiltration / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D009195:Peroxidase / Q000378:metabolism
chemical_list: D002619:Chemical Warfare Agents; C438646:S-2 (2-aminoethylamino)ethylphenylsulfide; D009195:Peroxidase; D005966:Glucuronidase; D004999:Amifostine; D009151:Mustard Gas
keywords: Amifostine; DRDE-07; chemical warfare agents; prophylactic; pulmonary; sulfur mustard