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达格列净:对抗顺铂诱导的Wistar大鼠肝毒性的一种有前景的策略。

Dapagliflozin: A Promising Strategy to Combat Cisplatin-Induced Hepatotoxicity in Wistar Rats.

作者信息

Satyam Shakta Mani, Bairy Laxminarayana Kurady, Rehman Abdul, Farook Mohamed, Khan Sofiya, Nair Anuradha Asokan, Binu Nirmal Nachiketh, Yehya Mohamed, Khan Mohammed Moin

机构信息

Faculty of Pharmacology, RAK College of Medical Sciences, RAK Medical and Health Sciences University, Ras Al Khaimah 11172, United Arab Emirates.

Faculty of Pathology, RAK College of Medical Sciences, RAK Medical and Health Sciences University, Ras Al Khaimah 11172, United Arab Emirates.

出版信息

Biology (Basel). 2024 Aug 29;13(9):672. doi: 10.3390/biology13090672.

Abstract

Recognizing the challenges posed by chemotherapy, specifically the hepatotoxic effects of drugs like cisplatin, this study aimed to examine the hepatoprotective potential of dapagliflozin to mitigate cisplatin-induced hepatotoxicity in a rat model. This study focused on repurposing drugs such as dapagliflozin and natural agents like silymarin as potential interventions to address cisplatin-induced hepatotoxicity. Thirty adult female Wistar rats were distributed into five groups and treated with cisplatin alone, silymarin, dapagliflozin, or a combination of dapagliflozin and silymarin accordingly for 45 days. Body weight, fasting blood glucose levels, liver function tests, and histopathological analysis were conducted to evaluate the hepatoprotective effects. Cisplatin-induced hepatotoxicity significantly ( < 0.05) increased the serum levels of ALT, AST, TB, and reduced the TP and albumin levels. Dapagliflozin administration led to significant reductions in ALT, AST, TB, and increased albumin levels. Silymarin demonstrated comparable effects. Combining dapagliflozin and silymarin showed synergistic effects, further reducing the liver enzymes and improving albumin levels. Histopathological examination supported these findings, revealing the restoration of liver structure with dapagliflozin and silymarin treatment. Dapagliflozin and silymarin exhibited substantial hepatoprotective benefits against cisplatin-induced hepatotoxicity in rats. The combination therapy demonstrated synergistic effects, highlighting a potential therapeutic approach for mitigating chemotherapy-induced liver damage. Further research into molecular mechanisms and clinical translation is warranted, offering hope for improved clinical outcomes in cancer patients undergoing cisplatin-based chemotherapy.

摘要

认识到化疗带来的挑战,特别是顺铂等药物的肝毒性作用,本研究旨在探讨达格列净减轻大鼠模型中顺铂诱导的肝毒性的肝保护潜力。本研究重点是将达格列净等药物和水飞蓟宾等天然药物重新用作解决顺铂诱导的肝毒性的潜在干预措施。将30只成年雌性Wistar大鼠分为五组,分别单独用顺铂、水飞蓟宾、达格列净或达格列净与水飞蓟宾的组合进行治疗,为期45天。进行体重、空腹血糖水平、肝功能测试和组织病理学分析以评估肝保护作用。顺铂诱导的肝毒性显著(<0.05)增加了血清谷丙转氨酶(ALT)、谷草转氨酶(AST)、总胆红素(TB)水平,并降低了总蛋白(TP)和白蛋白水平。给予达格列净导致ALT、AST、TB显著降低,白蛋白水平升高。水飞蓟宾表现出类似的效果。达格列净与水飞蓟宾联合使用显示出协同作用,进一步降低了肝酶水平并提高了白蛋白水平。组织病理学检查支持了这些发现,显示达格列净和水飞蓟宾治疗后肝脏结构得以恢复。达格列净和水飞蓟宾对大鼠顺铂诱导的肝毒性具有显著的肝保护作用。联合治疗显示出协同作用,突出了一种减轻化疗诱导的肝损伤的潜在治疗方法。有必要对分子机制和临床转化进行进一步研究,为接受基于顺铂化疗的癌症患者改善临床结局带来希望。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ac9/11428795/6dc6904e4081/biology-13-00672-g001.jpg

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