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Effect of infliximab, a tumor necrosis factor-alpha inhibitor, on doxorubicin-induced nephrotoxicity in rats

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Abstract

Treatment with the chemotherapeutic agent, doxorubicin (DOX), is limited by nephrotoxicity. We investigated the possible protective effect of infliximab, a tumor necrosis factor alpha (TNF-α) inhibitor on DOX-induced nephrotoxicity. Rats were treated with a single intraperitoneal (ip) injection of DOX (17.5 mg/kg) in the absence or presence of infliximab (5 mg/kg, i.p.). Plasma and urinary markers of kidney function, oxidative stress, and inflammation were measured. Kidney and heart tissue was evaluated histopathologically. DOX-induced nephrotoxicity was confirmed by increased plasma urea, creatinine, cystatin C, neutrophil gelatinase-associated lipocalin (NGAL), and clusterin concentrations. In addition, DOX increased urinary albumin/creatinine ratio, N-acetyl-β-D-glucosaminidase (NAG) activity, kidney injury molecule (KIM-1) concentrations, and reduced creatinine clearance. DOX significantly reduced renal antioxidants and increased plasma inflammatory markers and adiponectin concentrations. Concomitant treatment with infliximab did not significantly affect DOX-induced changes in plasma creatinine, cystatin C, or creatinine clearance. However, infliximab significantly reduced DOX-induced action on plasma urea, NGAL, clusterin, and adiponectin. Infliximab also significantly reduced urinary albumin/creatinine ratio, NAG activity, and KIM-1 concentrations, as well as the occurrence of fibrotic lesions in kidney tissue. Fibrosis detected in the heart was unchanged. In addition, infliximab reduced DOX-induced effects on plasma inflammatory markers, renal superoxide dismutase (SOD) and total antioxidant capacity. Our results show that infliximab is partially effective in mitigating DOX-induced nephrotoxicity in rats.

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Funding

Supported by a grant from Sultan Qaboos University (IG/MED//PHAR/16/02).

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Authors and Affiliations

  1. Department of Pharmacology and Clinical Pharmacy, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Oman

    Aly M. Abdelrahman, Yousuf M. Al Suleimani, Priyadarsini Manoj, Mohammed Ashique & Badreldin H. Ali

  2. Institute of Toxicology, Medical Faculty, University of Düsseldorf, Moorenstraße 5, 40225, Düsseldorf, Germany

    Nicole Schupp

Authors
  1. Aly M. Abdelrahman
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  2. Yousuf M. Al Suleimani
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  3. Priyadarsini Manoj
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  4. Mohammed Ashique
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  5. Badreldin H. Ali
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  6. Nicole Schupp
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Contributions

AA, YS, and BA designed research, participated in the interpretation of the results, wrote and reviewed the manuscript. NS performed the histological analysis, wrote and reviewed the manuscript. MA and PM conducted the experiments and analyzed. All authors read and approved the manuscript.

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Correspondence to Nicole Schupp.

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The authors declare that they have no conflict of interests.

Ethical approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures involving animals and their care were carried out in accordance with national and international laws and policies (EEC Council directives 2010/63/EU, 22 September, 2010 and NIH Guide for the Care and Use of Laboratory Animals, NIH Publications, 8th edition, 2011).

This article does not contain any studies with human participants performed by any of the authors.

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Abdelrahman, A.M., Al Suleimani, Y.M., Manoj, P. et al. Effect of infliximab, a tumor necrosis factor-alpha inhibitor, on doxorubicin-induced nephrotoxicity in rats. Naunyn-Schmiedeberg's Arch Pharmacol 393, 121–130 (2020). https://doi.org/10.1007/s00210-019-01719-x

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  • DOI: https://doi.org/10.1007/s00210-019-01719-x

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