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 |