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Protective effect of the nuclear factor kappa B inhibitor pyrrolidine dithiocarbamate in lung injury in rats with streptozotocin-induced diabetes.
Respiration. 2010; 79(5):402-10.R

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.

OBJECTIVES

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.

CONCLUSION

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+Show Affiliations

Department of Anesthesiology and Intensive Care, Bakirkoy Dr. Sadi Konuk Training and Research Hospital, Istanbul, Turkey.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

19996572

Citation

Eren, Gulay, et al. "Protective Effect of the Nuclear Factor Kappa B Inhibitor Pyrrolidine Dithiocarbamate in Lung Injury in Rats With Streptozotocin-induced Diabetes." Respiration; International Review of Thoracic Diseases, vol. 79, no. 5, 2010, pp. 402-10.
Eren G, Cukurova Z, Hergunsel O, et al. Protective effect of the nuclear factor kappa B inhibitor pyrrolidine dithiocarbamate in lung injury in rats with streptozotocin-induced diabetes. Respiration. 2010;79(5):402-10.
Eren, G., Cukurova, Z., Hergunsel, O., Demir, G., Kucur, M., Uslu, E., Dalo, E., Uhri, M., & Tugcu, V. (2010). Protective effect of the nuclear factor kappa B inhibitor pyrrolidine dithiocarbamate in lung injury in rats with streptozotocin-induced diabetes. Respiration; International Review of Thoracic Diseases, 79(5), 402-10. https://doi.org/10.1159/000264920
Eren G, et al. Protective Effect of the Nuclear Factor Kappa B Inhibitor Pyrrolidine Dithiocarbamate in Lung Injury in Rats With Streptozotocin-induced Diabetes. Respiration. 2010;79(5):402-10. PubMed PMID: 19996572.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Protective effect of the nuclear factor kappa B inhibitor pyrrolidine dithiocarbamate in lung injury in rats with streptozotocin-induced diabetes. AU - Eren,Gulay, AU - Cukurova,Zafer, AU - Hergunsel,Oya, AU - Demir,Guray, AU - Kucur,Mine, AU - Uslu,Ezel, AU - Dalo,Enis, AU - Uhri,Mehmet, AU - Tugcu,Volkan, Y1 - 2009/12/07/ PY - 2009/07/06/received PY - 2009/08/28/accepted PY - 2009/12/10/entrez PY - 2009/12/10/pubmed PY - 2010/7/16/medline SP - 402 EP - 10 JF - Respiration; international review of thoracic diseases JO - Respiration VL - 79 IS - 5 N2 - 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. OBJECTIVES: 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. CONCLUSION: 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. SN - 1423-0356 UR - https://www.unboundmedicine.com/medline/citation/19996572/Protective_effect_of_the_nuclear_factor_kappa_B_inhibitor_pyrrolidine_dithiocarbamate_in_lung_injury_in_rats_with_streptozotocin_induced_diabetes_ L2 - https://www.karger.com?DOI=10.1159/000264920 DB - PRIME DP - Unbound Medicine ER -