Department of Pharmacology, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, India.
Department of Biotechnology, Jamia Millia Islamia, New Delhi, India.
Exp Hematol. 2020 Feb;82:24-32. doi: 10.1016/j.exphem.2020.01.007. Epub 2020 Jan 24.
Cyclophosphamide (CP) is one of the commonly used anticancer drugs, but its use is limited by myelotoxicity. Nerolidol (NER) is a lipophilic, bioactive sesquiterpene reported to have neuroprotective, cardioprotective, gastroprotective, and renal protective potential, but its myeloprotective potential is underexplored. This study was aimed at evaluating the myeloid-protective potential of NER in CP-induced myelotoxic mice. NER 200 and 400 mg/kg was given orally from the first to the 14th day. CP 200 mg/kg was administered intravenously on the seventh day. At the end of the study, mice were humanly killed, and blood and bone marrow were collected and stored for hematologic, biochemical and histopathologic estimations. Bone marrow analysis revealed reduced bone marrow cellularity, α-esterase activity, colony-forming unit granulocyte-macrophage (CFU-GM) levels, colony-forming unit erythroid (CFU-E) levels, and burst-forming unit-erythroid (BFU-E) levels. Hematologic findings revealed reduced peripheral blood count and granulocyte-colony stimulating factor (G-CSF) levels, whereas biochemical analysis revealed increased malondialdehyde (MDA), tumor necrosis factor α (TNF-α), interleukin (IL)-6, and IL-1β levels and reduced superoxide dismutase (SOD), catalase (CAT), and IL-10 levels. Histopathologic study further strengthened our findings. Treatment with NER significantly reversed the hematotoxic and myelotoxic aberrations and retained the structural integrity of bone marrow. Findings of the current study suggest that NER is a potential therapeutic molecule that can mitigate CP-induced hematotoxic and myelotoxic manifestations. However, more detailed studies are needed to explicate the mechanism underlying its protective effect.
环磷酰胺(CP)是一种常用的抗癌药物,但由于其骨髓毒性而受到限制。橙花叔醇(NER)是一种亲脂性、生物活性的倍半萜烯,据报道具有神经保护、心脏保护、胃保护和肾保护作用,但对其骨髓保护作用的研究尚不足。本研究旨在评估 NER 在 CP 诱导的骨髓毒性小鼠中的骨髓保护潜力。NER 200 和 400mg/kg 从第 1 天到第 14 天口服给予。CP 200mg/kg 于第 7 天静脉注射。研究结束时,处死小鼠,采集血液和骨髓进行血液学、生化和组织病理学评估。骨髓分析显示骨髓细胞减少,α-酯酶活性、粒细胞-巨噬细胞集落形成单位(CFU-GM)水平、红细胞集落形成单位(CFU-E)水平和红细胞爆式形成单位(BFU-E)水平降低。血液学发现外周血计数和粒细胞集落刺激因子(G-CSF)水平降低,而生化分析显示丙二醛(MDA)、肿瘤坏死因子-α(TNF-α)、白细胞介素(IL)-6 和 IL-1β水平升高,超氧化物歧化酶(SOD)、过氧化氢酶(CAT)和 IL-10 水平降低。组织病理学研究进一步证实了我们的发现。NER 治疗显著逆转了血液毒性和骨髓毒性异常,并保持了骨髓的结构完整性。本研究的结果表明,NER 是一种潜在的治疗分子,可减轻 CP 诱导的血液毒性和骨髓毒性。然而,需要更多的详细研究来阐明其保护作用的机制。