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Effect of canagliflozin, a sodium glucose co-transporter 2 inhibitor, on cisplatin-induced nephrotoxicity in mice

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Abstract

Canagliflozin is a sodium glucose co-transporter 2 (SGLT2) inhibitor that is currently available for the management of type 2 diabetes mellitus. The present study investigated the effect of canagliflozin on cisplatin (CP)-induced nephrotoxicity in mice. The animals were divided into four groups (n = 6). The first and second groups received normal saline (control) and intraperitoneal (i.p.) cisplatin (20 mg/kg) on day 7, respectively. The third and fourth groups were given a single intraperitoneal (i.p.) injection of CP (20 mg/kg) on day 7 and canagliflozin (10 mg/kg/day) and (30 mg/kg/day), for 10 days, respectively. At day 11, animals were anesthetized and blood collected and kidneys were removed. CP significantly increased the plasma urea, creatinine, cystatin C, and clusterin concentrations and neutrophil gelatinase-associated lipocalin (NGAL) activity. In addition, CP increased urinary albumin/creatinine ratio, N-acetyl-β-D-glucosaminidase (NAG) activity, and liver-type fatty acid-binding protein (L-FABP) concentrations and reduced creatinine clearance. CP also significantly increased the plasma concentration of inflammatory cytokines [plasma tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1beta (IL-1β)] and significantly reduced antioxidant indices [catalase, glutathione reductase (GR), and superoxide dismutase (SOD)]. Histopathologically, CP caused a remarkable renal damage compared with control. Canagliflozin significantly ameliorated CP-induced biochemical and histopathological changes. The protective effect of canagliflozin is most likely due to anti-inflammatory and antioxidant effects. Our results show that administration of canagliflozin reversed the biochemical and histopathological indices of CP-induced nephrotoxicity in mice.

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Acknowledgements

We thank Ms. Halima Al Isaai for the help with the preparation of histopathology slides.

Funding

This study was supported by a grant from Sultan Qaboos University (IG/MED//PHAR/17/01).

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Authors and Affiliations

  1. Department of Pharmacology and Clinical Pharmacy, College of Medicine and Health Sciences, Sultan Qaboos University, PO Box 35, Al-Khod, 123, Muscat, Oman

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

  2. Department of Pathology, College of Medicine and Health Sciences, Sultan Qaboos University, PO Box 35, Al-Khod, Muscat, Oman

    Asem Shalaby

  3. Department of Physiology, College of Medicine and Health Sciences, United Arab Emirates University, P.O. Box 17666, Al Ain, UAE

    Abderrahim Nemmar

Authors
  1. Aly M. Abdelrahman
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  2. Yousuf Al Suleimani
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  3. Asem Shalaby
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  4. Mohammed Ashique
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  5. Priyadarsini Manoj
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  6. Abderrahim Nemmar
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  7. Badreldin H. Ali
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Contributions

A.N. and B.A. conceived and designed research.

A.A., Y.S., and A.N.; B.A. participated in the interpretation of the results, writing and review of the manuscript.

A.S. performed the histological analysis.

M.A. conducted the experiments and analysis of data.

P.M. conducted the experiments and analysis of data.

All authors read and approved the manuscript.

Corresponding author

Correspondence to Aly M. Abdelrahman.

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Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

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Informed consent was obtained from all individual participants included in the study.

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Abdelrahman, A.M., Al Suleimani, Y., Shalaby, A. et al. Effect of canagliflozin, a sodium glucose co-transporter 2 inhibitor, on cisplatin-induced nephrotoxicity in mice. Naunyn-Schmiedeberg's Arch Pharmacol 392, 45–53 (2019). https://doi.org/10.1007/s00210-018-1564-7

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  • DOI: https://doi.org/10.1007/s00210-018-1564-7

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