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Neuroprotective Potential of Berberine Against Doxorubicin-Induced Toxicity in Rat’s Brain

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Abstract

Chemotherapy-associated neurotoxicity is one of the principal side-effects for doxorubicin (DOX)-treated cancer patients. Despite its poor-penetration across the blood–brain barrier (BBB), DOX is linked to the induction of oxidative stress and neuroinflammation. Berberine (BEB) is a natural polyphenolic alkaloid, which exhibits unique antioxidant activity and anti-inflammatory potential. The present study was performed to investigate the neuroprotective potential of BEB in a rodent model of DOX-induced neurotoxicity. Neurotoxicity was induced in rats via a single acute dose of DOX (20 mg/kg/week, i.p.). BEB was administered at 50 mg/kg/day orally for 10 days before and 4 days after DOX administration. Brain acetylcholinesterase (AChE) activities were evaluated. Oxidative stress was investigated via the colorimetric determination of lipid peroxides, glutathione reduced (GSH) contents and catalase (CAT) activities in the brain tissue. In addition, DOX-induced genotoxicity was evaluated using comet assay. DOX produced a significant elevation in AChE activities. Additionally, DOX provoked oxidative stress as evidenced from the significant elevation in lipid peroxidation along with depletion in GSH contents and CAT activities. Moreover, DOX resulted in neuroinflammation as indicated by the elevation of pro-inflammatory mediator glial fibrillary acid protein (GFAP), as well as, the pro-apoptotic nuclear factor kappa B (NF-κB) and caspase-3 in brain tissue. Co-treatment with BEB significantly counteracted DOX-induced oxidative stress, neuroinflammation and genotoxicity. Histopathological and immunohistochemical examination supported the biochemical results. BEB demonstrated neuroprotective potential through exerting cholinergic, anti-oxidative, genoprotective, anti-inflammatory, and anti-apoptotic activities. Our findings present BEB as a promising “pre-clinical” neuroprotective agent against DOX-induced neurotoxicity during anti-neoplastic therapy.

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Data Availability

All data generated or analyzed during this study are included in this published article.

Abbreviations

DOX:

Doxorubicin

BBB:

Blood–brain barrier

BEB:

Berberine

AChE:

Acetylcholinesterase

GSH:

Glutathione reduced

CAT:

Catalase

GFAP:

Glial fibrillary acid protein

NF-κB:

Nuclear factor kappa B

ROS:

Reactive oxygen species

PUFAs:

Polyunsaturated fatty acids

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Authors and Affiliations

  1. Department of Therapeutic Chemistry, National Research Centre, 33 El-Bohouth St., Dokki, Cairo, 12622, Egypt

    Ghadha Ibrahim Fouad

  2. Pathology Department, Faculty of Veterinary Medicine, Cairo University, Giza, 12211, Egypt

    Kawkab A. Ahmed

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  1. Ghadha Ibrahim Fouad
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  2. Kawkab A. Ahmed
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Contributions

GIF conceived and designed the research proposal, performed experiments, analyzed biochemical data, and wrote the original manuscript. KAA was responsible for methodology and writing of histopathological and immunohistochemical investigations and review of the original manuscript.

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Correspondence to Ghadha Ibrahim Fouad.

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The animal protocol was adopted in accordance with the National Research Council’s Guide for the Care and Use of Laboratory Animals (NIH Publications No. 8023, revised 1978), and experimental procedures were approved by the Ethical Committee, National Research Centre (NRC), Egypt (Approval no. 19–313).

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Ibrahim Fouad, G., Ahmed, K.A. Neuroprotective Potential of Berberine Against Doxorubicin-Induced Toxicity in Rat’s Brain. Neurochem Res 46, 3247–3263 (2021). https://doi.org/10.1007/s11064-021-03428-5

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