小檗碱对阿霉素诱导的大鼠脑毒性的神经保护作用。
Neuroprotective Potential of Berberine Against Doxorubicin-Induced Toxicity in Rat's Brain.
机构信息
Department of Therapeutic Chemistry, National Research Centre, 33 El-Bohouth St., Dokki, Cairo, 12622, Egypt.
Pathology Department, Faculty of Veterinary Medicine, Cairo University, Giza, 12211, Egypt.
出版信息
Neurochem Res. 2021 Dec;46(12):3247-3263. doi: 10.1007/s11064-021-03428-5. Epub 2021 Aug 17.
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.
化疗相关性神经毒性是多柔比星（DOX）治疗癌症患者的主要副作用之一。尽管 DOX 很难穿透血脑屏障（BBB），但它与氧化应激和神经炎症的诱导有关。小檗碱（BEB）是一种天然多酚生物碱，具有独特的抗氧化活性和抗炎潜力。本研究旨在探讨 BEB 在 DOX 诱导的神经毒性啮齿动物模型中的神经保护潜力。通过单次腹腔注射 DOX（20mg/kg/周）诱导神经毒性。BEB 于 DOX 给药前 10 天和给药后 4 天每天口服 50mg/kg。评估大脑乙酰胆碱酯酶（AChE）活性。通过比色法测定脑组织中脂质过氧化物、还原型谷胱甘肽（GSH）含量和过氧化氢酶（CAT）活性来研究氧化应激。此外，通过彗星试验评估 DOX 诱导的遗传毒性。DOX 显著升高 AChE 活性。此外，DOX 引起氧化应激，表现为脂质过氧化显著升高，GSH 含量和 CAT 活性降低。此外，DOX 导致神经炎症，表现为促炎介质胶质纤维酸性蛋白（GFAP）升高，以及脑组织中核因子 kappa B（NF-κB）和半胱天冬酶-3（caspase-3）升高。BEB 联合治疗可显著拮抗 DOX 诱导的氧化应激、神经炎症和遗传毒性。组织病理学和免疫组织化学检查支持生化结果。BEB 通过发挥胆碱能、抗氧化、遗传保护、抗炎和抗凋亡作用显示出神经保护潜力。我们的研究结果表明，BEB 是一种有前途的“临床前”神经保护剂，可用于抗肿瘤治疗期间对抗 DOX 诱导的神经毒性。
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