Protective effect of the nuclear factor kappa B inhibitor pyrrolidine dithiocarbamate in lung injury in rats with streptozotocin-induced diabetes.
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.
Eren
Gulay
G
Department of Anesthesiology and Intensive Care, Bakirkoy Dr. Sadi Konuk Training and Research Hospital, Istanbul, Turkey.
Cukurova
Zafer
Z
Hergunsel
Oya
O
Demir
Guray
G
Kucur
Mine
M
Uslu
Ezel
E
Dalo
Enis
E
Uhri
Mehmet
M
Tugcu
Volkan
V
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
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