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

  • Mohamed M. Abdel-DaimEmail author
  • Lotfi Aleya
  • Badr E. El-Bialy
  • Abdelrahman Ibrahim AbushoukEmail author
  • Saad Alkahtani
  • Saud Alarifi
  • Abdullah A. Alkahtane
  • Gadah AlBasher
  • Daoud Ali
  • Rafa S. Almeer
  • Nouf K. Al-Sultan
  • Jawahir Alghamdi
  • Abeer Alahmari
  • Simona G. Bungau
Research Article


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.


Ceftriaxone Cisplatin Rats α-Tocopherol Vitamin E 





cis-diamminedichloroplatinum II




Glutathione peroxidase


Reduced glutathione




Nitric oxide


Reactive oxygen species


Superoxide dismutase


Total antioxidant capacity


Tumor necrosis factor-α


Vitamin E



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 source

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

Compliance with ethical standards

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.

Conflicts 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 2019

Authors and Affiliations

  1. 1.Pharmacology Department, Faculty of Veterinary MedicineSuez Canal UniversityIsmailiaEgypt
  2. 2.Chrono-Environnement Laboratory, UMR CNRS 6249Bourgogne Franche-Comté UniversityBesançon CedexFrance
  3. 3.Department of Forensic Medicine and Toxicology, Faculty of Veterinary MedicineSadat City UniversitySadat CityEgypt
  4. 4.Faculty of MedicineAin Shams UniversityCairoEgypt
  5. 5.Department of Zoology, Science CollegeKing Saud UniversityRiyadhSaudi Arabia
  6. 6.Department of Biology, Science CollegeKing Khalid UniversityAbhaSaudi Arabia
  7. 7.Department of Pharmacy, Faculty of Medicine and PharmacyUniversity of OradeaOradeaRomania

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