Department of Medical Elementology and Toxicology, Jamia Hamdard (Hamdard University), Hamdard Nagar, New Delhi 110062, India.
Department of Medical Elementology and Toxicology, Jamia Hamdard (Hamdard University), Hamdard Nagar, New Delhi 110062, India.
Biomed Pharmacother. 2017 Oct;94:418-429. doi: 10.1016/j.biopha.2017.07.124. Epub 2017 Aug 1.
Oxidative stress-related inflammation and apoptosis are important pathogenic consequences, which result in acute pulmonary toxicity. Bleomycin (BLM) is used to treat various forms of cancers. However, its prolonged administration is associated with major toxicity to respiratory system. We studied the effect of walnut (Juglans regia) extract in a rat model of BLM-induced pulmonary toxicopathy. We also studied parameters of inflammation, apoptosis and oxidative stress in various groups of animals. Prophylactic treatment of total methanolic extract of walnut at the dose of 150mg/kg b.w. was given per os to Wistar rats for 14days prior to BLM exposure. A single intratracheal injection of BLM (10U/kg b.w.) was administered on the eleventh day of the treatment. There was a marked increase in the hydroxyproline level, lipid peroxidation, nitric oxide production, and in the activities of xanthine oxidase and myeloperoxidase in the lung tissue in BLM-treated animals when compared to control animals. BLM also decreased the activities of antioxidant enzymes such as glutathione reductase and catalase and increased the lung inflammation and apoptosis by upregulating the NF-κB signaling pathway and caspase-3 expression. Treatment with walnut extract attenuated these changes in a significant manner. Walnut extract significantly modulated the lung injury as measured by markers of cellular injury such as lactate dehydrogenase and alkaline phosphatase, total cell count, total protein and reduced glutathione in bronchoalveolar lavage fluid. Histological findings supported the protective effects of walnut extract against BLM-induced lung injury. Walnut which has been shown to have numerous medicinally valuable constituents including ellagic acid showed efficacy in preventing the various toxicopathological effects of BLM in rat lungs. Overall, walnut extract decreases BLM-induced oxidative stress and lung inflammation by modulating the alveolar macrophage inflammatory response in rats and thus protecting them from the pathological effect of BLM.
氧化应激相关的炎症和细胞凋亡是重要的发病机制，导致急性肺毒性。博来霉素（BLM）用于治疗各种形式的癌症。然而，其长期给药与呼吸系统的主要毒性有关。我们研究了核桃（Juglans regia）提取物在 BLM 诱导的肺毒性大鼠模型中的作用。我们还研究了各组动物的炎症、凋亡和氧化应激参数。在 BLM 暴露前 14 天，用 150mg/kg bw 的核桃总甲醇提取物经口预防性治疗 Wistar 大鼠。在治疗的第 11 天，通过气管内注射 BLM（10U/kg bw）。与对照组相比，BLM 处理的动物肺组织中的羟脯氨酸水平、脂质过氧化、一氧化氮产生、黄嘌呤氧化酶和髓过氧化物酶活性显著增加。BLM 还通过上调 NF-κB 信号通路和 caspase-3 表达，降低了谷胱甘肽还原酶和过氧化氢酶等抗氧化酶的活性，并增加了肺炎症和细胞凋亡。核桃提取物的治疗显著减轻了这些变化。核桃提取物显著调节了肺损伤，如通过细胞损伤标志物如乳酸脱氢酶和碱性磷酸酶、总细胞计数、总蛋白和还原型谷胱甘肽来衡量。组织学发现支持了核桃提取物对 BLM 诱导的肺损伤的保护作用。核桃含有多种具有药用价值的成分，包括鞣花酸，证明其在预防 BLM 在大鼠肺部的各种毒性病理作用方面有效。总体而言，核桃提取物通过调节肺泡巨噬细胞炎症反应，减少 BLM 诱导的氧化应激和肺部炎症，从而保护大鼠免受 BLM 的病理作用。
