Protective Role of Epigallocatechin Gallate in a Rat Model of Cisplatin-Induced Cerebral Inflammation and Oxidative Damage: Impact of Modulating NF-κB and Nrf2

  • Manar Hamed Arafa
  • Hebatallah Husseini AtteiaEmail author
Original Article


Cisplatin is a widely used chemotherapeutic agent in treating various types of cancers. However, it can induce neurotoxicity and nephrotoxicity, limiting its dose and clinical use. Although previous studies indicated the direct link between cisplatin-induced central neurotoxicity and oxidative stress, the exact mechanism is not completely understood. Therefore, herein we investigated the effects of prophylactic and concurrent treatment with (−)-epigallocatechin-3-gallate (EGCG), a natural polyphenolic neuroprotective antioxidant, on cisplatin-induced brain toxicity in rats to delineate its molecular mechanism of action. We found that cisplatin initiated a cascade of genetic, biological, and histopathological changes in the brain cortex, inducing inflammatory cytokines, appearance of scattered inflammatory cells, nitro-oxidative stress, and apoptotic proteins in the cerebral cortex. However, EGCG not only protected against cisplatin-induced inflammatory burden but also ameliorated the induction of nitro-oxidative stress and apoptotic proteins triggered by cisplatin in the cerebral cortex of pre- and co-treated rats with respect to their unprotected counterparts. EGCG anti-inflammatory effect here may be attributed to the downregulation of nuclear factor kappa B (NF-κB). Additionally, this natural polyphenol significantly ameliorated cisplatin-elicited reduction in cerebral cortex brain-derived neurotrophic factor and acetylcholine esterase. Upregulation of nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream heme oxygenase-1 (HO-1) by EGCG prophylactic and concurrent administration here seems also to play a key role in the protective impact of EGCG against cisplatin toxicity through enhancing total antioxidant capacity. Thus, EGCG can be used as a promising prophylactic adjuvant for preventing the development of brain inflammation and oxidative damage associated with cisplatin chemotherapy.


Acetylcholine esterase Apoptosis Brain-derived neurotrophic factor (BDNF) Cisplatin (−)-Epigallocatechin-3-gallate Oxidative damage Proinflammatory cytokines 


Compliance with Ethical Standards

All animal manipulations and treatments were conducted precisely in conformation with the National Institutes of Health (NIH) Recommendations for the Care and Use of Laboratory Animals.

Conflict of Interest

The authors declare that they have no conflict of interest.


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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Forensic Medicine and Clinical Toxicology, Faculty of MedicineZagazig UniversityZagazigEgypt
  2. 2.Department of Biochemistry, Faculty of PharmacyZagazig UniversityZagazigEgypt

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