title: Protective effects of melatonin and S-methylisothiourea on mechlorethamine induced nephrotoxicity.
abstract: BACKGROUND
  In this study, we aimed to investigate the protective effects of melatonin (MEL) and S-methylisothiourea (SMT) on mechlorethamine (MEC) induced nephrotoxicity.
  
  
  METHODS
  A total of 36 male Sprague-Dawley rats were divided into four groups: control, MEC, MEC+MEL, and MEC+SMT. Three groups received single dose of MEC (3.5 mg/kg) via transdermal route. Control animals were given saline only 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
  The tissue TNF-α, IL-1β, and NOx levels were found significantly different for all groups (P < 0.001). MEC application resulted in severe histopathological changes. Melatonin showed meaningful protection against kidney damage. But protection by SMT was weaker. TNF-α and IL-1β levels increased significantly with MEC application, and MEL and SMT ameliorated these increases in kidney tissue. MEC also elevated NOx levels in kidney tissue.
  
  
  CONCLUSIONS
  Both inflammation and oxidative stress may have an important role in the MEC induced nephrotoxicity. MEL and SMT may also have anti-inflammatory properties, as well as anti-oxidant properties.
authors.affiliation: Department of CBRN Defense, Gulhane Military Medical Academy, Ankara, Turkey.
authors.forename: Zeki Ilker
authors.initials: ZI
authors.lastname: Kunak
authors.forename: Enis
authors.initials: E
authors.lastname: Macit
authors.forename: Hakan
authors.initials: H
authors.lastname: Yaren
authors.forename: Halil
authors.initials: H
authors.lastname: Yaman
authors.forename: Erdinc
authors.initials: E
authors.lastname: Cakir
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Aydin
authors.forename: Turker
authors.initials: T
authors.lastname: Turker
authors.forename: Yasemin Gulcan
authors.initials: YG
authors.lastname: Kurt
authors.forename: Ayhan
authors.initials: A
authors.lastname: Ozcan
authors.forename: Bulent
authors.initials: B
authors.lastname: Uysal
authors.forename: Salim
authors.initials: S
authors.lastname: Isbilir
authors.forename: Emin Ozgur
authors.initials: EO
authors.lastname: Akgul
authors.forename: Tuncer
authors.initials: T
authors.lastname: Cayci
authors.forename: Ahmet
authors.initials: A
authors.lastname: Korkmaz
authors.forename: Levent
authors.initials: L
authors.lastname: Kenar
mesh_terms: D000818:Animals; D002619:Chemical Warfare Agents / Q000633:toxicity*; D004195:Disease Models, Animal; D007249:Inflammation / Q000517:prevention & control; D007550:Isothiuronium / Q000031:analogs & derivatives* / Q000627:therapeutic use; D007674:Kidney Diseases / Q000139:chemically induced / Q000517:prevention & control*; D008297:Male; D008466:Mechlorethamine / Q000633:toxicity*; D008550:Melatonin / Q000627:therapeutic use*; D018384:Oxidative Stress / Q000187:drug effects; D020011:Protective Agents / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D002619:Chemical Warfare Agents; D020011:Protective Agents; D007550:Isothiuronium; D008466:Mechlorethamine; C027744:S-methylisothiopseudouronium; D008550:Melatonin