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Effects of dapagliflozin in experimental sepsis model in rats.

Ulusal travma ve acil cerrahi dergisi = Turkish journal of trauma & emergency surgery : TJTES (2019-05-29)
Zehra Betül Kingir, Zarife Nigar Özdemir Kural, Muhammet Emin Cam, Ozlem Tugce Cilingir, Turgut Şekerler, Feriha Ercan, Özlem Bingöl Özakpınar, Derya Ozsavci, Mesut Sancar, Betul Okuyan
ABSTRACT

The aim of this study was to evaluate the possible protective effects of dapagliflozin in an experimental sepsis model in rats. 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. 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. 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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Caspase 9 Colorimetric Activity Assay Kit, LEHD, Caspase-9 Colorimetric Activity Assay Kits provide a simple & convenient means for assaying the activity of caspases that recognize the LEHD.
Sigma-Aldrich
Dapagliflozin propanediol monohydrate, ≥98% (HPLC)
Sigma-Aldrich
Dapagliflozin, ≥98% (HPLC)