Department of Histology and Embryology, Faculty of Medicine, Firat University, Elazig, Turkey.
Department of Medical Biology, Faculty of Medicine, Firat University, Elazig, Turkey.
Int J Med Mushrooms. 2023;25(1):1-12. doi: 10.1615/IntJMedMushrooms.2022046311.
Doxorubicin (DOX), a broad spectrum chemotherapeutic, has toxic effects on healthy tissues. Mitochondrial processes and oxidative stress act in the DOX-induced toxicity, therefore antioxidant therapies are widely used. The study was aimed to evaluate the therapeutic potential of Pleurotus eryngii extract (PEE), an extract of a fungus with antioxidant properties, against DOX-induced lung damage. Rats were divided into Control, DOX, DOX + PEE, and PEE groups (n = 6). DOX was administered intraperitoneally in a single dose (10 mg/kg BW) and PE (200 mg/kg BW) was administered by oral gavage every other day for 21 days. Histopathological evaluations, immunohistochemical analyses, total oxidant status (TOS)/total antioxidant status (TAS) method, and quantitative real-time polymerase chain reaction (qRT-PCR) analysis were performed. DOX led to severe histopathological disruptions in rat lungs. Also, DOX remarkably increased the expression of dynamin 1 like (DRP1) and decreased the expression of mitofusin 1 (MFN1) and mitofusin 2 (MFN2) genes, which are related to mitochondrial dynamics. Moreover, DOX caused an increase in TOS/ TAS and 8-hydroxy-2-deoxyguanosine (8-OHdG) levels. On the other hand, PEE treatment remarkably normalized the histopathological findings, mitochondrial dynamics-related gene expressions, markers of oxidative stress, and DNA damage. The present study signs out that PEE can ameliorate the DOX-mediated lung toxicity and the antioxidant mechanism associated with mitochondrial dynamics can have a role in this potent therapeutic effect.
多柔比星(DOX)是一种广谱化疗药物,对健康组织有有毒作用。线粒体过程和氧化应激在 DOX 诱导的毒性中起作用,因此抗氧化治疗被广泛应用。本研究旨在评估具有抗氧化特性的真菌提取物杏鲍菇提取物(PEE)对 DOX 诱导的肺损伤的治疗潜力。大鼠分为对照组、DOX 组、DOX+PEE 组和 PEE 组(n=6)。DOX 腹腔内单次给药(10mg/kg BW),PEE(200mg/kg BW)每隔一天灌胃给药,共 21 天。进行组织病理学评价、免疫组织化学分析、总氧化剂状态(TOS)/总抗氧化状态(TAS)方法和定量实时聚合酶链反应(qRT-PCR)分析。DOX 导致大鼠肺部严重的组织病理学破坏。此外,DOX 显著增加了与线粒体动力学相关的 dynamin 1 样(DRP1)的表达,降低了线粒体融合蛋白 1(MFN1)和线粒体融合蛋白 2(MFN2)的表达。此外,DOX 导致 TOS/TAS 和 8-羟基-2-脱氧鸟苷(8-OHdG)水平升高。另一方面,PEE 治疗显著使组织病理学发现、线粒体动力学相关基因表达、氧化应激标志物和 DNA 损伤正常化。本研究表明,PEE 可以改善 DOX 介导的肺毒性,与线粒体动力学相关的抗氧化机制可能在这种有效的治疗作用中发挥作用。