Ulus Travma Acil Cerrahi Derg. 2019; 25(3): 213-221 | DOI: 10.5505/tjtes.2018.82826

Effects of dapagliflozin in experimental sepsis model in rats

Zehra Betül Kingir¹, Zarife Nigar Özdemir Kural², Muhammet Emin Cam³, Ozlem Tugce Cilingir⁴, Turgut Þekerler⁵, Feriha Ercan⁴, Özlem Bingöl Özakpýnar⁵, Derya Ozsavci⁵, Mesut Sancar¹, Betul Okuyan^1
1Department of Clinical Pharmacy, Marmara University Faculty of Pharmacy, Ýstanbul-Turkey
²Department of Physiology, Marmara University Faculty of Medicine, Ýstanbul-Turkey
³Department of Pharmacology, Marmara University Faculty of Pharmacy, Ýstanbul-Turkey
⁴Department of Histology and Embryology, Marmara University Faculty of Medicine, Ýstanbul-Turkey
⁵Department of Biochemistry, Marmara University Faculty of Pharmacy, Ýstanbul-Turkey

BACKGROUND: The aim of this study was to evaluate the possible protective effects of dapagliflozin in an experimental sepsis model in rats.
METHODS: Saline (1 mL/kg, p.o.) or dapagliflozin (10 mg/kg, p.o.) was administered to Sprague-Dawley rats for 5 days prior to the surgical procedures. Under anesthesia, sepsis was induced by cecal ligation puncture, while sham control groups underwent laparotomy only. Blood urea nitrogen, creatinine, and glucose levels were measured in serum samples and the levels of malondialdehyde (MDA), glutathione (GSH), myeloperoxidase (MPO), tumor necrosis factor alpha, interleukin 1 beta, caspase 8, and caspase 9 were determined in tissue samples (kidney, liver, and lung). Histological evaluation was also performed.
RESULTS: The administration of dapagliflozin in a sepsis model reduced oxidative stress (MDA), increased antioxidant levels (GSH), and reduced inflammation (MPO) in the kidney (p<0.05). Dapagliflozin also decreased oxidative stress (MDA) in lung tissue and decreased inflammation (MPO) in lung and liver tissue (p<0.05). Caspase 8 and 9 levels in kidney, lung, and liver tissue were increased (p<0.05) in the dapagliflozin group compared with the sepsis group. According to the histopathological results, sepsis was moderately improved in renal tissue and slightly attenuated in lung and liver tissue with the administration of dapagliflozin.
CONCLUSION: Dapagliflozin had a preventive effect on sepsis-induced kidney damage, but the protective effect was mild in lung and liver tissue in the present study.

Keywords: Apoptosis, dapagliflozin; inflammation; oxidative stress; sepsis.

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Dapagliflozin’in sýçanlarda deneysel sepsis modeli üzerine etkileri

Zehra Betül Kingir¹, Zarife Nigar Özdemir Kural², Muhammet Emin Cam³, Ozlem Tugce Cilingir⁴, Turgut Þekerler⁵, Feriha Ercan⁴, Özlem Bingöl Özakpýnar⁵, Derya Ozsavci⁵, Mesut Sancar¹, Betul Okuyan^1
1Marmara Üniversitesi Eczacýlýk Fakültesi, Klinik Eczacýlýk Anabilim Dalý, Ýstanbul
²Marmara Üniversitesi Týp Fakültesi, Fizyoloji Anabilim Dalý, Ýstanbul
³Marmara Üniversitesi Eczacýlýk Fakültesi, Farmakoloji Anabilim Dalý, Ýstanbul
⁴Marmara Üniversitesi Týp Fakültesi, Histoloji ve Embriyoloji Anabilim Dalý, Ýstanbul
⁵Marmara Üniversitesi Eczacýlýk Fakültesi, Biyokimya Anabilim Dalý, Ýstanbul

AMAÇ: Bu çalýþmada, sýçanlarda dapagiflozinin deneysel sepsis modeli üzerindeki olasý koruyucu etkilerinin deðerlendirilmesi amaçlandý.
GEREÇ VE YÖNTEM: Sprague-Dawley sýçanlara cerrahi operasyonlarýn 5 gün öncesinde serum fizyolojik (1 mL/kg, p.o.) veya dapagliflozin (10 mg/kg, p.o.) verilmeye baþlandý. Sepsis, anestezi altýnda, çekal ligasyon ve perforasyon modeli ile oluþturulurken, sham kontrol gruplarýna sadece laparotomi yapýldý. Serumda BUN, kreatinin ve glukoz düzeyleri; dokularda (böbrek, karaciðer ve akciðer) ise MDA, GSH, MPO, TNF-α, IL-1β, kaspaz 8 ve kaspaz 9 düzeyleri belirlendi. Bu dokularda histolojik deðerlendirme de yapýldý.
BULGULAR: Sepsiste dapagliflozin uygulamasý, böbrek dokularýnda oksidatif stresi (MDA) azalttý, antioksidan düzeyleri (GSH) arttýrdý ve enflamasyonu (MPO) azalttý (p<0.05). Sepsiste dapagliflozin uygulamasý akciðer dokularýnda oksidatif stresi (MDA) azalttý, akciðer ve karaciðer dokularýnda ise enflamasyonu (MPO) azalttý (p<0.05). Ayrýca, böbrek, akciðer ve karaciðer dokularýnda kaspaz 8 ve 9 düzeylerini arttýrdý (p<0.05). Histopatolojik sonuçlara göre, dapagliflozin uygulamasý böbrek dokularýnda orta derece; akciðer ve karaciðer dokularýnda ise hafif iyileþtirdi.
TARTIÞMA: Bu çalýþmada, dapagliflozinin deneysel sepsis modelinde böbrek hasarýný önleyici etkisinin olduðu gösterilmesine raðmen akciðer ve karaciðer dokularý üzerine hafif koruyucu etkisi olduðu bulunmuþtur.

Anahtar Kelimeler: Apoptoz, dapagliflozin; enflamasyon; oksidatif stres; sepsis.

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