Q4 Pharmacology, Toxicology and Pharmaceutics Hacettepe University Journal of the Faculty of Pharmacy Pub Date : 2023-08-19 DOI:10.52794/hujpharm.1171489
Tuğçe Boran, Bahar ULUS KARACA, Ayça KARAGÖZ KÖROĞLU, Feriha Ercan, Gülcan Özhan
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摘要

Dapagliflozin (DAPA)是一种钠葡萄糖共转运蛋白2 (SGLT2)抑制剂,是治疗2型糖尿病的一种治疗选择。尽管几项研究已经证明了它对肾脏的保护作用,但FDA警告说,dapa有引起肾毒性的风险。SGLT2抑制剂的作用机制可能导致肾脏氧化应激和炎症。本研究旨在阐明DAPA对肾脏的分子作用。雄性大鼠高脂饮食两周后,单次注射STZ (35 mg/kg b.w)引发链脲佐菌素(STZ)诱导的糖尿病。糖尿病大鼠按10 mg/kg b.w给予DAPA,灌胃28 d。在肾脏匀浆中评价DAPA的氧化应激、炎症和细胞凋亡诱导电位。组织学检查观察细胞形态变化及细胞凋亡情况。观察到,DAPA处理降低了氧化参数。糖尿病对照组炎症介质增加,但这种增加被DAPA治疗轻微抑制。组织学检查显示,DAPA改善了糖尿病引起的改变和细胞凋亡。由此可见,DAPA通过减轻氧化应激、抑制炎症和细胞凋亡对肾脏具有保护作用。然而,需要进一步的研究来确定DAPA对糖尿病患者肾脏的长期影响,关注不同的机制和个体差异。
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Dapagliflozinin Diyabetik Sıçanlarda Sub-akut Maruziyet Sonrası Renal Etkilerinin Değerlendirilmesi
Dapagliflozin (DAPA), a sodium glucose co-transporter 2 (SGLT2) inhibitor, is a therapy option for the treatment of type 2 diabetes. Although several studies have demonstrated its protective effects on the kidney, the FDA warns about the risk of DAPA-induced nephrotoxicity. SGLT2 inhibitors may induce oxidative stress and inflammation in the kidney due to their mechanism of action. In the present study, it was aimed to clarify the molecular effects of DAPA on the kidney. Streptozotocin (STZ)-induced diabetes was initiated by single injection of STZ (35 mg/kg b.w.) after a two-week high-fat diet in male rats. Diabetic rats were administered with DAPA at 10 mg/kg b.w., by oral gavage for 28 days. The oxidative stress, inflammation and apoptosis induction potentials of DAPA were evaluated in kidney homogenates. The morphological changes and apoptosis were investigated by histological examinations. It was observed that DAPA treatment reduced oxidative parameters. The inflammatory mediators increased in diabetic control group, however, this increase was slightly inhibited by DAPA treatment. According to the histological examinations, DAPA ameliorated the diabetes-induced changes and apoptosis. As a result, DAPA showed a protective effect on the kidney by alleviating oxidative stress and inhibiting inflammation and apoptosis. However, further studies are needed to determine the long-term effects of DAPA on the kidney in diabetics by focusing on different mechanisms and individual differences.
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来源期刊
Hacettepe University Journal of the Faculty of Pharmacy
Hacettepe University Journal of the Faculty of Pharmacy Pharmacology, Toxicology and Pharmaceutics-Pharmacology, Toxicology and Pharmaceutics (all)
CiteScore
0.60
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0.00%
发文量
18
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