title: Protective effect of the nuclear factor kappa B inhibitor pyrrolidine dithiocarbamate in lung injury in rats with streptozotocin-induced diabetes.
abstract: BACKGROUND
  Diabetes mellitus (DM) causes debilitating complications and, as a result, diabetics frequently require intensive care. Although lungs are not thought to be affected primarily by DM, an increasing number of studies indicate physiological and structural abnormalities in diabetic lungs.
  
  
  OBJECTIVE
  Pyrrolidine dithiocarbamate (PDTC) is a metal chelator and a potent inhibitor of NF-kappaB. Keeping in mind that NF-kappaB activation may be crucial in end-organ injury due to DM, we studied the role of PDTC on the inhibition of NF-kappaB activation and its effects on possible lung injury in rats with streptozotocin-induced DM.
  
  
  METHODS
  36 Sprague-Dawley rats were allocated into 4 groups: diabetes, diabetes + PDTC, control and control + PDTC. At the end of 10 weeks, rats were sacrificed and their lungs were taken for histopathological and immunohistochemical evaluation [for NF-kappaB (p65) and endothelial nitric oxide (eNOS) immunoreactivities]. Protein carbonyl content (PCC), superoxide dismutase (SOD) and reduced glutathione (GSH) activities were measured.
  
  
  RESULTS
  Histopathologically, basal membranes were thickened and there was intense inflammatory reaction in diabetic lungs. However, the PDTC group, in which there were poor positive expressions of eNOS and p65 activity compared to diabetes group, revealed fewer inflammatory changes. PCC levels in diabetic lungs were higher, but SOD and GSH activities were lower. However, measurements of these parameters in the PDTC group and controls gave similar results.
  
  
  CONCLUSIONS
  Lungs are exposed to changes induced by oxidative stress in diabetes through NF-kappaB activation and PDTC seems to be useful to prevent diabetic lung injury.
authors.affiliation: Department of Anesthesiology and Intensive Care, Bakirkoy Dr. Sadi Konuk Training and Research Hospital, Istanbul, Turkey.
authors.forename: Gulay
authors.initials: G
authors.lastname: Eren
authors.forename: Zafer
authors.initials: Z
authors.lastname: Cukurova
authors.forename: Oya
authors.initials: O
authors.lastname: Hergunsel
authors.forename: Guray
authors.initials: G
authors.lastname: Demir
authors.forename: Mine
authors.initials: M
authors.lastname: Kucur
authors.forename: Ezel
authors.initials: E
authors.lastname: Uslu
authors.forename: Enis
authors.initials: E
authors.lastname: Dalo
authors.forename: Mehmet
authors.initials: M
authors.lastname: Uhri
authors.forename: Volkan
authors.initials: V
authors.lastname: Tugcu
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D007150:Immunohistochemistry; D008168:Lung / Q000378:metabolism / Q000473:pathology; D055370:Lung Injury / Q000209:etiology* / Q000517:prevention & control*; D008566:Membranes / Q000473:pathology; D008853:Microscopy; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D009569:Nitric Oxide / Q000378:metabolism; D050050:Protein Carbonylation; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism; D013859:Thiocarbamates / Q000494:pharmacology*; D051996:Transcription Factor RelA / Q000378:metabolism
chemical_list: D000975:Antioxidants; D016328:NF-kappa B; D011759:Pyrrolidines; C498145:Rela protein, rat; D013859:Thiocarbamates; D051996:Transcription Factor RelA; C020972:pyrrolidine dithiocarbamic acid; D009569:Nitric Oxide; D013482:Superoxide Dismutase; D005978:Glutathione