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Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 391, Issue 11, pp 1247–1255 | Cite as

Perindopril regulates the inflammatory mediators, NF-κB/TNF-α/IL-6, and apoptosis in cisplatin-induced renal dysfunction

  • Abdel-Gawad S. Shalkami
  • Mohamed I. A. Hassan
  • Ahmed A. Abd El-Ghany
Original Article
  • 113 Downloads

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.

Keywords

Cisplatin Perindopril Nephrotoxicity Inflammation Apoptosis 

Notes

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.

Authors’ contribution

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.

Compliance with ethical standards

All animals’ procedures in this work were conducted according to the Animal Ethics Committee, Faculty of Medicine, Assiut University, Egypt.

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Abdel-Gawad S. Shalkami
    • 1
  • Mohamed I. A. Hassan
    • 1
  • Ahmed A. Abd El-Ghany
    • 2
  1. 1.Department of Pharmacology and Toxicology, Faculty of PharmacyAl-Azhar UniversityAssiutEgypt
  2. 2.Department of Biochemistry, Faculty of PharmacyAl-Azhar UniversityAssiutEgypt

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