Ameliorative Effect of Empagliflozin and Linagliptin on Cisplatin-Induced Nephrotoxicity and Cardiotoxicity
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Date
2025-03-13
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Saudi Digital Library
Abstract
يعد السيسبالتين أحد أكثر أدوية العالج الكيميائي فعالية والتي تستخدم لعالج أنواع مختلفة من السرطان. ومع ذلك، فإن استخدامه مقيد
بسبب آثاره الجانبية مثل السمية العصبية، والسمية الكلوية، وسمية القلب. إن تطور مثبطات ناقل الصوديوم الجلوكوز 2- )2SGLT)،
ومثبطات ديببتيدايل بيبتيديز 4- ) i-4DPP )في عالج داء السكري من النوع الثاني يوفر خيا ًرا جديدًا لتحسين السمية المرتبطة بعالج
السيسبالتين. تم توثيق التأثيرات الوقائية لإلمباجليفلوزين )i2SGLT )والليناجليبتين )i-4DPP )على وظائف القلب واألوعية الدموية
والكلى جيدًا. أن إمباجليفلوزين وليناجليبتين قد يخففان من سمية القلب والكلى المرتبطة بالعالج بالسيسبالتين.
لذلك ستقوم هذه الدراسة بتقييم التأثيرات الوقائية لإلمباجليفلوزين والليناجليبتين ضد إصابة القلب والكلى الناجمة عن السيسبالتين،
ولتقييم ما إذا كان مزيج إمباغليفلوزين والليناجليبتين يعمالن بشكل تآزري لتعديل وظائف الكلى والقلب واألوعية الدموية بعد تناول
السيسبالتين، ولتحديد اآللية الجزيئية للسيسبالتين على الجسم. السمية الكلوية وسمية القلب .
إلى سبع مجموعات متساوية على النحو
سيتم استخدام تسع واربعون من فئران ويستار الذكور في هذه الدراسة وتقسيمهم عشوائياً
التالي: مجموعة المتحكمة، مجموعة السيسبالتين، 10ملجم/كجم إمباغليفلوزين و إمباغليفلوزين مع سيسبالتين3، ملجم/كجم ليناجليبتين
، ليناجليبتين مع سيسبالتين، إمباجليفلوزين وليناجليبتين عن طريق الفم باإلضافة إلى سيسبالتين لمدة 10 يوم ، وفي اليوم االول يتم
حقن سيسبالتين 20 ملغم/كغم في منطقة الغشاء البريتوني مرة واحدة .
ا
سيتم تقييم المؤشرات الحيوية الكلوية، والمؤشرات الحيوية للقلب، ومعلمات اإلجهاد التأكسدي. سيتم تحليل عينات القلب والكلى بحثً
عن اإلجهاد التأكسدي.
Background: The therapeutic usage of cisplatin, an extremely efficient chemotherapeutic drug, was constrained by its adverse impact on various organs, including the heart and kidneys. Evidence showed that new antidiabetic medications improve cardiorenal function in non-diabetic and diabetic clients. This study aims to assess the ameliorative outcome of linagliptin and empagliflozin (each solely and in combination) on cisplatin-induced cardiorenal toxicity in non-diabetic rats. Methods: Forty nine rats were indiscriminately distributed into seven equal groups: Control (saline 10 ml /kg), Cisplatin group (CP 20 mg/kg), Empagliflozin group (EMPA10 mg/kg), Linagliptin group (LINA 3 mg/kg) and treated groups of (CP + EMPA, CP+LINA, CP+EMPA+LINA). All groups were treated by oral route for 10 days, and CP (20 mg/kg single intraperitoneal dose) was administered to the treated groups. Samples of blood were collected from the retro-orbital plexus for evaluation of biochemical parameters such as Creatinine, blood urea nitrogen (BUN), creatine kinase (CK-MB), lactate dehydrogenase (LDH), and troponin I. Animals hearts and kidneys were extracted to evaluate the activity of malonaldehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX) Results: The results showed a noteworthy rise in Creatinine, BUN, LDH, CK-MB, troponin I and MDA in the CP group in compared with the control. In contrast, treated groups (CP+LINA, CP+EMPA, CP+LINA+EMPA) exhibited a notable reduction in CRE, BUN, LDH, CK-MB, troponin I and MDA in comparison with CP group. Furthermore, SOD, GPX, and CAT levels were significantly decreased in CP group (in both cardiac and kidney tissues) in comparison with the control. While, the same parameters (SOD, GPX, and CAT) were considerably rise in the treated groups in comparison with CP group except that CP+LINA group revealed a non-notable increase in cardiac SOD and CAT Conclusion: This study revealed that empagliflozin and linagliptin (solely and in combination) improved cardiorenal function and oxidative stress biomarkers in rats treated with cisplatin, which may reflect their ameliorative effect on cardiorenal toxicity induced by cisplatin. Therefore, they could be promising approaches to mitigate cardiorenal damage associated with cisplatin treatment.
Background: The therapeutic usage of cisplatin, an extremely efficient chemotherapeutic drug, was constrained by its adverse impact on various organs, including the heart and kidneys. Evidence showed that new antidiabetic medications improve cardiorenal function in non-diabetic and diabetic clients. This study aims to assess the ameliorative outcome of linagliptin and empagliflozin (each solely and in combination) on cisplatin-induced cardiorenal toxicity in non-diabetic rats. Methods: Forty nine rats were indiscriminately distributed into seven equal groups: Control (saline 10 ml /kg), Cisplatin group (CP 20 mg/kg), Empagliflozin group (EMPA10 mg/kg), Linagliptin group (LINA 3 mg/kg) and treated groups of (CP + EMPA, CP+LINA, CP+EMPA+LINA). All groups were treated by oral route for 10 days, and CP (20 mg/kg single intraperitoneal dose) was administered to the treated groups. Samples of blood were collected from the retro-orbital plexus for evaluation of biochemical parameters such as Creatinine, blood urea nitrogen (BUN), creatine kinase (CK-MB), lactate dehydrogenase (LDH), and troponin I. Animals hearts and kidneys were extracted to evaluate the activity of malonaldehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX) Results: The results showed a noteworthy rise in Creatinine, BUN, LDH, CK-MB, troponin I and MDA in the CP group in compared with the control. In contrast, treated groups (CP+LINA, CP+EMPA, CP+LINA+EMPA) exhibited a notable reduction in CRE, BUN, LDH, CK-MB, troponin I and MDA in comparison with CP group. Furthermore, SOD, GPX, and CAT levels were significantly decreased in CP group (in both cardiac and kidney tissues) in comparison with the control. While, the same parameters (SOD, GPX, and CAT) were considerably rise in the treated groups in comparison with CP group except that CP+LINA group revealed a non-notable increase in cardiac SOD and CAT Conclusion: This study revealed that empagliflozin and linagliptin (solely and in combination) improved cardiorenal function and oxidative stress biomarkers in rats treated with cisplatin, which may reflect their ameliorative effect on cardiorenal toxicity induced by cisplatin. Therefore, they could be promising approaches to mitigate cardiorenal damage associated with cisplatin treatment.
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Keywords
: Cisplatin, Empagliflozin, Linagliptin, oxidative stress biomarkers, Cardiorenal toxicity