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The ameliorative effects of ceftriaxone and vitamin E against cisplatin-induced nephrotoxicity

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Abstract

Nephrotoxicity is a common adverse effect of treatment with cisplatin (CDDP). This study was performed to evaluate the antioxidant and nephroprotective efficacy of ceftriaxone (CTX) and vitamin E (Vit.E), alone and in combination against CDDP-induced acute renal injury. Fifty-six male albino rats were equally divided into seven groups, receiving (I) normal saline, (II) CTX (100 mg/kg, intraperitoneal [i.p] injection), (III) Vit.E (100 mg/kg orally), (IV) CDDP (5 mg/kg i.p injection), (V) CDDP plus CTX, (VI) CDDP plus Vit.E, and (VII) CDDP plus CTX in combination with Vit.E. All treatments were administered daily for 10 days except CDDP, which was given as a single dose at the sixth day of the study. Compared to normal control rats, CDDP-injected rats showed significantly (p < 0.05) higher serum levels of renal injury biomarkers (uric acid, urea, and creatinine) and tumor necrosis factor-α (TNF-α), as well as increased renal tissue concentrations of malondialdehyde, nitric oxide, and TNF-α. Moreover, CDDP administration was associated with significantly lower (p < 0.05) renal tissue levels of reduced glutathione and activities of endogenous antioxidant enzymes (glutathione peroxidase, superoxide dismutase, and catalase) and total antioxidant capacity. All these alterations were significantly ameliorated in CDDP-injected rats, receiving CTX and/or Vit.E, compared to rats receiving CDDP alone. Interestingly, the antioxidant and anti-inflammatory effects were more marked in the CTX-Vit.E combination group, compared to groups receiving either drug alone. In conclusion, CTX and Vit.E (especially in combination) could counteract the nephrotoxic effect of CDDP, probably through their antioxidant activities.

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Abbreviations

CAT:

Catalase

CDDP:

cis-diamminedichloroplatinum II

CTX:

Ceftriaxone

GPx:

Glutathione peroxidase

GSH:

Reduced glutathione

MDA:

Malondialdehyde

NO:

Nitric oxide

ROS:

Reactive oxygen species

SOD:

Superoxide dismutase

TAC:

Total antioxidant capacity

TNF-α:

Tumor necrosis factor-α

Vit.E:

Vitamin E

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Acknowledgments

The authors would like to thank the Deanship of Scientific Research at King Saud University for funding this work through Research Group no. RGP-018.

Funding

This work was supported by the Deanship of Scientific Research at King Saud University, Saudi Arabia (Grant No: RGP-018).

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Authors and Affiliations

  1. Pharmacology Department, Faculty of Veterinary Medicine, Suez Canal University, Ismailia, 41522, Egypt

    Mohamed M. Abdel-Daim

  2. Chrono-Environnement Laboratory, UMR CNRS 6249, Bourgogne Franche-Comté University, 25030, Besançon Cedex, France

    Lotfi Aleya

  3. Department of Forensic Medicine and Toxicology, Faculty of Veterinary Medicine, Sadat City University, Sadat City, Egypt

    Badr E. El-Bialy

  4. Faculty of Medicine, Ain Shams University, Ramsis St, 11566, Abbasia, Cairo, Egypt

    Abdelrahman Ibrahim Abushouk

  5. Department of Zoology, Science College, King Saud University, Riyadh, Saudi Arabia

    Saad Alkahtani, Saud Alarifi, Abdullah A. Alkahtane, Gadah AlBasher, Daoud Ali, Rafa S. Almeer, Nouf K. Al-Sultan & Jawahir Alghamdi

  6. Department of Biology, Science College, King Khalid University, Abha, Saudi Arabia

    Abeer Alahmari

  7. Department of Pharmacy, Faculty of Medicine and Pharmacy, University of Oradea, Oradea, Romania

    Simona G. Bungau

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  1. Mohamed M. Abdel-Daim
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Corresponding authors

Correspondence to Mohamed M. Abdel-Daim or Abdelrahman Ibrahim Abushouk.

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The Research Ethical Committee at Suez Canal University approved our experimental protocol (approval no. 20147). All animal stress conditions were taken into consideration and hardly avoided.

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The authors declare that they have no conflict of interest.

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Abdel-Daim, M.M., Aleya, L., El-Bialy, B.E. et al. The ameliorative effects of ceftriaxone and vitamin E against cisplatin-induced nephrotoxicity. Environ Sci Pollut Res 26, 15248–15254 (2019). https://doi.org/10.1007/s11356-019-04801-2

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