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Pantoprazole abrogated cisplatin-induced nephrotoxicity in mice via suppression of inflammation, apoptosis, and oxidative stress

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Abstract

The current study was designed to evaluate the potential abatement effect of pantoprazole against cisplatin-induced nephrotoxicity and establishing the possible protective mechanisms. Thirty-two male mice were allocated for treatment with saline, single dose of cisplatin (10 mg/kg/i.p), pantoprazole (30 mg/kg/once daily) for 5 days or combination of pantoprazole and cisplatin for 5 days. Urine, blood, and both kidneys were collected for further evaluations. Pantoprazole significantly countermand cisplatin-induced disfigurement of renal histology, kidney weight to body weight ratio, serum levels of creatinine and urea, and microalbuminuria. Furthermore, pantoprazole mostly normalized cisplatin-induced distortion of renal levels of inflammatory cytokines (tumor necrosis factor-alpha, interleukin-6, interleukin-10) and renal content of apoptosis regulating protein expressions (Bax, Bcl2, and active caspase 3). In addition, pantoprazole significantly subsided cisplatin-induced distortion of renal lipid peroxidation marker (MDA), renal superoxide dismutase, and catalase activities and renal reduced glutathione content. This study provides an evidence for the protective utility of short-term pantoprazole against cisplatin-induced nephrotoxicity in mice. The protective mechanism of pantoprazole could be through diminution of cisplatin-induced inflammation, oxidative stress, and their subsequent apoptotic renal cell death via abatement of apoptosis regulating protein expressions (Bax, Bcl2, and active caspase3).

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Acknowledgments

We are greatly thankful to both Prof. Adel Kholoussy (Professor of Pathology, Cairo University, Egypt) and Dr. Sayed Abdel Raheem (Associate professor of histology, Al-Azhar University, Egypt) for their contribution in the histopathological examination.

Funding

The authors disclosed individual full financial support and funding for this study. The authors disclosed personal financial support from authors MSE and MHH.

Author information

RI, MSE, and MHH conceived and designed research, provided the necessary tools and reagents, acquired and validated data. MSE and MHH provided the funding and drafted the manuscript. RI conducted most of the experiments. MSE performed the formal statically analysis. MHH reviewed, edited, and submitted the manuscript. All authors read and approved the manuscript.

Correspondence to Memy H. Hassan.

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Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in our study involving animals were in accordance with the ethical standards and guidelines from Ethics Committee of the Experimental Animal Care Society, Al-Azhar University, Cairo, Egypt, and Taibah University, Kingdom of Saudi Arabia. In addition, all applicable international and national, guidelines for the care, and use of animals were followed. The protocol approval number is phr._Med. Research_ Protective. Trial. Anticancer. Drugs. Organs. Toxicity. Mice. 0000007

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Ismail, R.S., El-Awady, M.S. & Hassan, M.H. Pantoprazole abrogated cisplatin-induced nephrotoxicity in mice via suppression of inflammation, apoptosis, and oxidative stress. Naunyn-Schmiedeberg's Arch Pharmacol (2020) doi:10.1007/s00210-020-01823-3

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Keywords

  • Cisplatin
  • Pantoprazole
  • Nephrotoxicity
  • Oxidative stress
  • Inflammation
  • Apoptosis