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The role of urotensin-II and its receptors in sepsis-induced lung injury under diabetic conditions    
Yazarlar
Rüstem Anıl Uğan
Atatürk Üniversitesi, Türkiye
Elif Çadırcı
Atatürk Üniversitesi, Türkiye
Zekai Halıcı
Atatürk Üniversitesi, Türkiye
Erdem Toktay
Kafkas Üniversitesi, Türkiye
Doç. Dr. İrfan ÇINAR
Kafkas Üniversitesi, Türkiye
Özet
This study aimed to investigate the potential role of urotensin-II receptors in sepsis-induced lung injury in diabetic mice using urotensin-II receptor agonists and antagonists. A total of 110 male CD1 mice were used in this study. Diabetes was induced by 200 mg/kg streptozotocin. One month after diabetes induction, the cecal ligation and puncture-induced polymicrobial sepsis model was applied in the diabetic and non-diabetic mice. Low and high doses of human urotensin-II agonist (HU-II) and antagonist (palosuran) were administered one hour after sepsis induction. HU-II administration was repeated in two-hour intervals. Blood and tissue samples were collected at 6 and 12H after sepsis induction for biochemical, molecular, and histopathologic examinations. Regarding to the lungs mRNA expression and immunohistochemistry results of TNF-α, IL1 β, IL6, and NF-κB, it was observed that cytokine levels significantly increased in the diabetes group and the sepsis groups compared to the healthy group; this increase was significantly higher in the diabetes-sepsis groups. Our biochemical (superoxide dismutase, glutathione, and malondialdehyde) and histopathological findings in the lungs also supported these results. All increased parameters were significantly reduced dose-dependently by the administration of palosuran, an urotensin receptor antagonist. mRNA expression of urotensin-II and its receptor were examined in the lung tissue. Palosuran administration significantly reduced the urotensin-II and urotensin-II receptor levels that increased in the damaged tissue. This study has shown that urotensin-II and urotensin-II receptors contribute to the aggravation of sepsis-induced lung injury in diabetic mice; palosuran prevents this damage by antagonizing urotensin-II receptors.
Anahtar Kelimeler
Diabetes | Lung | Mice | Palosuran | Sepsis | Urotensin-II
Makale Türü Özgün Makale
Makale Alt Türü SSCI, AHCI, SCI, SCI-Exp dergilerinde yayımlanan tam makale
Dergi Adı European Journal of Pharmacology
Dergi ISSN 0014-2999
Dergi Tarandığı Indeksler SCI-Expanded
Makale Dili İngilizce
Basım Tarihi 01-2018
Cilt No 818
Sayı 818
Sayfalar 457 / 469
Doi Numarası 10.1016/j.ejphar.2017.11.011