title: The protective effect of melatonin and S-methylisothiourea treatments in nitrogen mustard induced lung toxicity in rats.
abstract: OBJECTIVE
  Mustard is highly toxic to the lung. Its toxic effects are associated with inflammatory cell accumulation and increased pro-inflammatory cytokines as well as reactive oxygen and nitrogen species. In this study, we aimed to investigate the efficiency of melatonin (MEL) and S-methylisothiourea (SMT) on mechlorethamine (MEC) induced lung toxicity.
  
  
  METHODS
  Thirty-six male rats were randomly divided into four groups: control, MEC, MEC+MEL, and MEC+SMT. Control group was given saline only via transdermal route. Other groups were exposured to a single dose of MEC (3.5 mg/kg) via transdermal route. MEL (100 mg/kg) was administered intraperitoneally 30 min after the application of MEC, and after the same dose of MEL was given every 12 h for a total of six doses. SMT (50 mg/kg) was also given intraperitoneally 30 min after the application of MEC.
  
  
  RESULTS
  MEC injection resulted in alveolar epithelial injury, hemorrhage, inflammation, edema and interalveolar septal thickening in the lung tissues. The tissue TNF-α, IL-1β, and nitrate/nitrite (NOx) levels were found significantly different for all groups (p<0.001). TNF-α and IL-1β levels increased significantly with MEC exposure, and MEL and SMT ameliorated these increases in lung tissues. MEC also elevated NOx levels in lung tissue. Melatonin showed meaningful protection against lung injury. But protection of SMT was weaker.
  
  
  CONCLUSIONS
  Inflammation plays an important role in the MEC induced lung toxicity as well as oxidative and nitrosative stress. Melatonin has also anti-inflammatory properties similar to SMT, as well as anti-oxidant properties. But melatonin treatment was found more efficient than SMT treatment.
authors.affiliation: Department of Toxicology, Gulhane Military Medical Academy, Etlik, Ankara, Turkey. Electronic address: enis@gata.edu.tr.
authors.forename: Enis
authors.initials: E
authors.lastname: Macit
authors.forename: Hakan
authors.initials: H
authors.lastname: Yaren
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Aydin
authors.forename: Zeki Ilker
authors.initials: ZI
authors.lastname: Kunak
authors.forename: Halil
authors.initials: H
authors.lastname: Yaman
authors.forename: Onder
authors.initials: O
authors.lastname: Onguru
authors.forename: Bulent
authors.initials: B
authors.lastname: Uysal
authors.forename: Ahmet
authors.initials: A
authors.lastname: Korkmaz
authors.forename: Samet
authors.initials: S
authors.lastname: Turel
authors.forename: Levent
authors.initials: L
authors.lastname: Kenar
mesh_terms: D000818:Animals; D002619:Chemical Warfare Agents / Q000633:toxicity*; D053583:Interleukin-1beta / Q000378:metabolism; D007550:Isothiuronium / Q000031:analogs & derivatives* / Q000494:pharmacology; D008168:Lung / Q000473:pathology; D008171:Lung Diseases / Q000139:chemically induced* / Q000473:pathology; D008297:Male; D008466:Mechlorethamine / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D008550:Melatonin / Q000494:pharmacology*; D011014:Pneumonia / Q000139:chemically induced / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D026361:Reactive Nitrogen Species / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D002619:Chemical Warfare Agents; D053583:Interleukin-1beta; D026361:Reactive Nitrogen Species; D014409:Tumor Necrosis Factor-alpha; D007550:Isothiuronium; D008466:Mechlorethamine; C027744:S-methylisothiopseudouronium; D008550:Melatonin
keywords: Inflammation; Lung toxicity; Mechlorethamine; Melatonin; Pro-inflammatory cytokines; S-Methylisothioure