Egyptian Propolis Extract Attenuates Hepatotoxicity Induced by Doxorubicin via Increasing Antioxidant Defense and Decreasing Inflammatory and Apoptotic Markers: Targeting Nrf2 and Bcl-2

Ahmed Almeldin, Reham Younis, Rowida Ibrahim, S. Motawea, Mai Mwafy, Haidy Khattab
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Abstract

Doxorubicin (DOX) is a chemotherapy medication that is used to treat different types of cancers. Propolis is commonly used as a hepatoprotective agent against oxidative stress. Therefore, the present study was designed to investigate the possible protective role of the Egyptian propolis extract (EPE) against DOX-induced hepatic toxicity in rats. The study was carried out on forty male adult albino rats divided into four groups (control group): received normal saline by oral gavage daily for 28, (EPE group): received EPE (200 mg /kg) daily by oral gavage for 28 days. (DOX group): rats were injected once with DOX (20 mg/kg) intraperitoneally on the 24th day (EPE treated DOX group): received EPE (200 mg /kg) daily by oral gavage for 28 days and injected with DOX 20 mg/kg intraperitoneally on the 24th day. Our results revealed that liver enzymes, MDA, TNFα, interleukin -1β (IL-1β) and IL-6 and caspase-3 were significantly increased in DOX group compared with control, while EPE treated DOX group showed significant decrease. Catalase and superoxide dismutase were significantly decreased in DOX group compared with control while EPE treated DOX group showed significant increase. Moreover, gene expression of TNF α, nuclear factor erythroid 2–related factor 2 (NRF-2), heme oxygenase -1 (HO-1) have been elevated significantly in DOX group when compared with control and their mRNA levels have been downregulated significantly by EPE treatment while EPE treatment has upregulated gene expression of BCL-2. Conclusion: our results raised the idea that EPE protecting the liver from DOX-related oxidative and apoptotic effects.
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埃及蜂胶提取物通过提高抗氧化防御能力和降低炎症及凋亡标记物减轻多柔比星诱导的肝毒性:靶向 Nrf2 和 Bcl-2
多柔比星(DOX)是一种化疗药物,用于治疗不同类型的癌症。蜂胶通常被用作抗氧化压力的保肝剂。因此,本研究旨在调查埃及蜂胶提取物(EPE)对大鼠 DOX 引起的肝毒性可能起到的保护作用。研究以 40 只雄性成年白化大鼠为对象,分为四组(对照组):每天口服生理盐水,连续 28 天;(EPE 组):每天口服 EPE(200 毫克/千克),连续 28 天。(EPE处理DOX组:每天口服EPE(200毫克/千克),共28天,第24天腹腔注射DOX(20毫克/千克);EPE处理DOX组:每天口服EPE(200毫克/千克),共28天,第24天腹腔注射DOX(20毫克/千克)。结果显示,与对照组相比,DOX组肝酶、MDA、TNFα、白细胞介素-1β(IL-1β)、IL-6和Caspase-3显著升高,而EPE处理的DOX组显著降低。与对照组相比,DOX 组的过氧化氢酶和超氧化物歧化酶明显降低,而 EPE 处理的 DOX 组则明显升高。此外,与对照组相比,DOX 组 TNF α、核因子红细胞 2 相关因子 2(NRF-2)、血红素加氧酶-1(HO-1)的基因表达明显升高,EPE 处理后其 mRNA 水平明显下调,而 EPE 处理后 BCL-2 的基因表达上调。结论:我们的研究结果提出了一种观点,即 EPE 可保护肝脏免受 DOX 相关氧化和凋亡效应的影响。
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