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首页> 外文期刊>Biochemical Pharmacology >A new combination of sitagliptin and furosemide protects against remote myocardial injury induced by renal ischemia/reperfusion in rats
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A new combination of sitagliptin and furosemide protects against remote myocardial injury induced by renal ischemia/reperfusion in rats

机译：SitaGliptin和呋塞米的新组合保护了大鼠肾缺血/再灌注诱导的远程心肌损伤

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Acute kidney injury (AKI) is associated with high mortality resulting from extra-renal organ damage, particularly the heart. The present study aimed to investigate the protective effect of sitagliptin, a dipeptidyl peptidase-4 (DPP4) inhibitor, against renal and remote cardiac damage induced by ischemia/reperfusion (IR), a leading cause of AKI. In this attempt, we compared the effects of sitagliptin to furosemide, a loop diuretic. Furosemide is commonly used clinically in AKI however, there is a lack of evidence regarding its beneficial effects in AKI. In addition, the combined administration of both drugs was also investigated. Ischemia was induced in anesthetized male Wistar rats by occluding both renal pedicles for 30 min followed by reperfusion for 24 h. Sitagliptin (5 mg kg(-1)), furosemide (245 mg kg-1) or their combination were administered orally at 5 h post-IR and 2 h before euthanasia. Administration of sitagliptin or furosemide ameliorated renal and cardiac deterioration induced by renal IR. This was manifested as significant reduction of serum creatinine, urea, cystatin c, creatine kinase-MB, cardiac troponin-I and lactate dehydrogenase (P < 0.05). Drug treatment significantly inhibited IR-induced elevation of TNF-alpha, NF-kappa B and caspase-3 (P < 0.05) in kidney and heart tissue. In addition, they significantly suppressed malondialdehyde, NO and iNOS content, whereas they increased glutathione and antioxidative enzymes activity (P < 0.05) in both tissues. Interestingly, a superior protection was observed with the combination compared to the individual drugs. We assume that this combination represents a promising regimen for managing AKI, particularly with the poor clinical outcome obtained with furosemide alone. (C) 2015 Elsevier Inc. All rights reserved.
机译：急性肾损伤（AKI）与肾脏器官损伤的高死亡率有关，特别是心脏。本研究旨在研究SITAGLIPTIN，二肽肽酶-4（DPP4）抑制剂，抗缺血/再灌注（IR）诱导的肾病和偏远心脏损伤的保护作用，是AKI的主要原因。在这种尝试中，我们将SitaGlittin对呋塞米的影响进行了比较，一种环路利尿剂。呋塞米常用于AKI临床上，缺乏有关其在AKI有益效果的证据。此外，还研究了两种药物的组合给药。通过封闭肾椎弓体30分钟，然后再灌注24小时，在麻醉的雄性Wistar大鼠中诱导缺血。 SITAGLIPTIN（5mg kg（-1）），呋塞米（245mg kg-1）或它们的组合在术后5小时和2小时之前口服给药。肾红外诱导的SitaGlitiN或呋塞米改善肾癌和心脏劣化。这表现为血清肌酐，尿素，胱抑素C，肌酸激酶-MB，心肌肌钙蛋白-1和乳酸脱氢酶的显着减少（P <0.05）。药物治疗显着抑制肾脏和心脏组织中TNF-α，NF-Kappa B和Caspase-3（P <0.05）的IR诱导的升高。此外，它们显着抑制了丙二醛，NO和INOS含量，而它们在两种组织中增加了谷胱甘肽和抗氧化酶活性（P <0.05）。有趣的是，与个体药物相比，用组合观察到优异的保护。我们假设这种组合代表了管理AKI的有希望的方案，特别是单独用呋塞米获得的临床结果不良。 （c）2015 Elsevier Inc.保留所有权利。

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