Department of Immunology, Amala Cancer Research Centre, Amala Nagar, Thrissur, 680555 Kerala, India.
Inflammopharmacology. 2010 Aug;18(4):197-207. doi: 10.1007/s10787-010-0042-8. Epub 2010 May 15.
Cyclophosphamide (CTX) is a widely used antineoplastic drug, which could cause toxicity to normal cells due to its toxic metabolites. The use of CTX in treating cancer patients is limited due to its severe toxicity induced mainly by oxidative stress. The present study reports the protective role of Vernonia cinerea L. against the CTX-induced toxicity in Balb/c mice. Intraperitoneal administration of the extract significantly increased the total WBC Count, bone marrow cellularity, alpha-esterase positive cells, and weights of lymphoid organs in CTX-treated animals, when compared with CTX control mice. Administration of V. cinerea was found to reduce the enhanced level of alkaline phosphatase, glutamate pyruvate transaminase, lipid peroxidation, and also significantly increased the reduced glutathione level in CTX-treated animals. Histopathological analysis of small intestine also suggests that extract could reduce the CTX-induced intestinal damage. The level of proinflammatory cytokine TNF-alpha, which was elevated during CTX administration, was significantly reduced by the V. cinerea extract administration. The lowered levels of other cytokines like IFN-gamma, IL-2, GM-CSF, after CTX treatment were also found to be increased by extract administration. Administration of V. cinerea did not compromise the anti-neoplastic activity of CTX. Infact, there was a synergistic action of CTX and V. cinerea in reducing the solid tumors in mice. Methanolic extract of V. cinerea given intraperitoneally (i.p.) showed a significant chemoprotective activity without compromising the chemotherapeutic efficacy of CTX, indicating its possible use as an adjuvant during chemotherapy.
环磷酰胺(CTX)是一种广泛应用的抗肿瘤药物,由于其有毒代谢物,会对正常细胞造成毒性。由于其主要由氧化应激引起的严重毒性,CTX 在癌症患者中的使用受到限制。本研究报道了 Vernonia cinerea L. 对 CTX 诱导的 Balb/c 小鼠毒性的保护作用。与 CTX 对照组小鼠相比,腹腔内给予该提取物可显著增加 CTX 处理动物的总白细胞计数、骨髓细胞数、α-酯酶阳性细胞和淋巴器官重量。发现 Vernonia cinerea 的给药可降低碱性磷酸酶、谷氨酸丙酮酸转氨酶、脂质过氧化的增强水平,并显著增加 CTX 处理动物中还原型谷胱甘肽的水平。小肠的组织病理学分析也表明,提取物可减轻 CTX 引起的肠道损伤。在 CTX 给药期间升高的促炎细胞因子 TNF-α的水平,通过 Vernonia cinerea 提取物的给药显著降低。还发现,在用 CTX 处理后降低的其他细胞因子(如 IFN-γ、IL-2、GM-CSF)的水平也通过提取物给药而增加。Vernonia cinerea 的给药不会影响 CTX 的抗肿瘤活性。事实上,CTX 和 Vernonia cinerea 的联合给药在减少小鼠的实体瘤方面具有协同作用。腹腔内给予 Vernonia cinerea 的甲醇提取物显示出显著的化学保护活性,而不影响 CTX 的化学治疗功效,表明其在化疗期间可能用作辅助剂。