Abstract
Cisplatin (CP) is an essential chemotherapeutic drug used over the world against many types of cancer. It has several side effects such as ototoxicity, myelosuppression, and nephrotoxicity. Nephrotoxicity is the most dangerous and is considered a dose-limiting one. Oxidative stress, inflammation, and apoptosis are involved in this toxicity. This study was conducted to focus on the impact of perindopril (PER) against CP-induced nephrotoxicity in rat. Male albino rats were divided to control, rats received a single dose of CP, rats received PER, and rats co-received PER and CP. Nephrotoxicity evoked by CP challenge was characterized histologically and biochemically including significant increase in relative kidney/body weight ratio and serum urea and creatinine. Additionally, CP markedly increased renal tissue content of malondialdehyde (MDA) while decreased reduced glutathione (GSH) and depleted glutathione-S-transferase (GST) activity. CP produced significant increase in the inflammation biomarkers; nuclear factor-κB (NF-κB), tumor necrosis factor-α (TNF-α), and interlukine-6 (IL-6). Administration of CP clearly upregulated caspase-3, while it downregulated B-cell lymphoma-2 (BCL-2) gene expressions. Perindopril treatment showed a significant restoration in the pathological alterations histologically and biochemically, which are provoked by CP administration. Altogether, these results suggested a good therapeutic role of PER against CP-induced nephrotoxicity through its influence on oxidative stress, inflammation, and apoptosis pathway.
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Acknowledgements
The authors are grateful to Prof. Dr. Dr. Kawkab A. Ahmed, Professor of Pathology, Faculty of Veterinary Medicine, Cairo University, Egypt, for her kind help in performing the histopathological examination.
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AS Shalkami and MIA Hassan conceived and designed this research. All the authors conducted experiments. AS Shalkami and AA Abd El-Ghany analyzed data. AS Shalkami and MIA Hassan wrote the manuscript. All the authors read and approved the manuscript.
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All animals’ procedures in this work were conducted according to the Animal Ethics Committee, Faculty of Medicine, Assiut University, Egypt.
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Shalkami, AG.S., Hassan, M.I.A. & Abd El-Ghany, A.A. Perindopril regulates the inflammatory mediators, NF-κB/TNF-α/IL-6, and apoptosis in cisplatin-induced renal dysfunction. Naunyn-Schmiedeberg's Arch Pharmacol 391, 1247–1255 (2018). https://doi.org/10.1007/s00210-018-1550-0
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DOI: https://doi.org/10.1007/s00210-018-1550-0