环磷酰胺（CP）是最广泛使用的抗肿瘤药物之一，但这种药物引起的肾毒性是其使用的主要限制因素。Nerolidol（NERO）是一种天然生物活性化合物，具有多种药理作用。使用HK-2肾细胞和瑞士白化小鼠进行了体外和体内研究。细胞系和动物经过NERO 25和50µM + CP 30µM处理（体外），NERO从第1天到第15天+ CP 200mg/kg, 第17天以单次腹腔注射给予NERO 400mg/kg，i.p. CP （体内）。对氧化应激标志物、肾特异性损伤标志物、炎症、凋亡、纤维化和组织病理学改变进行了研究。研究结果显示，在NERO 400与CP 200相比，体内研究中丙二醛水平和白细胞介素-6显著降低（p < 0.01），肿瘤坏死因子-α、IL-1β水平显著降低（p < 0.001），超氧化物歧化酶、过氧化氢酶、谷胱甘肽和白细胞介素-10水平显著增加（p < 0.01）。体外研究显示，在NERO 50µM处理时，与30µM处理相比，核因子kappa-B轻链增强因子激活的B细胞、裂解的caspase-3、肾损伤分子-1和转化生长因子-β1的表达都减少（p < 0.001），而NERO 25µM仅减少了裂解的caspase-3的水平（p < 0.05）。NERO 400还降低了尿酸（p < 0.05）、尿素（p < 0.01）、血尿素氮和血清肌酐水平（p < 0.001），增加了血尿素氮/肌酐比值（p < 0.001）。此外，转化生长因子-β1、透明质酸（p < 0.01）、4-羟基脯氨酸、Masson三色染色中富含胶原的区域和Smad3表达的水平也显著降低（p < 0.001）。此外，多种肾脏染色的结果显示，在NERO 400处理时，结构逆转异常、厚基底膜和糖原水平朝向正常方向减少。因此，该研究展示了NERO对环磷酰胺引起的肾毒性的新机制。该研究的结果可以被认为是向缓解使用环磷酰胺治疗的患者所引起的肾毒性发展辅助治疗的一步。

Cyclophosphamide (CP) is one of the most extensively used antineoplastic drug, but the nephrotoxicity caused by this drug is a major limiting factor for its use. Nerolidol (NERO) is a natural bioactive compound with diverse pharmacological actions. In Vitro and in vivo study was performed using HK-2 renal cells and Swiss Albino mice. Cell lines and animals were treated with NERO 25 and 50 µM + 30 µM CP (in vitro), 200 and 400 mg/kg, p.o. NERO from day 1 to day 15 + 200 mg/kg, i.p. CP on day 17 as single intraperitoneal injection (in vivo). The makers of oxidative stress, renal-specific injury markers, inflammation, apoptosis, fibrosis, and histopathological changes were studied. The study's outcome showed a significant reduction in the level of malonaldehyde and interleukin-6 (p < 0.01), tumor necrosis factor-α, IL-1β (p < 0.001), and an increase in the superoxide dismutase, catalase, glutathione and interleukin-10 level (p < 0.01), in the in vivo study when treated with NERO 400 and compared with CP 200. In Vitro study showed reduced expression of nuclear factor kappa light chain enhancer of activated B cells, cleaved caspase-3, kidney injury molecule-1 and transforming growth factor-β-1 (p < 0.001), when treated with NERO 50 µM whereas NERO 25 µM only reduced the level of cleaved caspase-3 (p < 0.05) when compared with 30 µM. NERO 400 also reduced uric acid (p < 0.05), urea (p < 0.01), blood urea nitrogen, and serum creatinine levels (p < 0.001) and increased the level of blood-urea-nitrogen/creatinine ratio (p < 0.001). Additionally, the level of fibrosis-specific markers such as transforming growth factor-β1, hyaluronic acid (p < 0.01), 4-hydroxyproline, a collagen-rich area in Masson's' trichome stain, and Smad3 expression was also significantly reduced (p < 0.001). Furthermore, the outcome of multiple renal staining showed structural reversal aberrations, reduction of the thick basement membrane, and glycogen level toward normal when treated with NERO 400. Thus, the study showed a novel mechanistic modality of NERO against cyclophosphamide-induced renal toxicity. The outcome of this study can be considered a step closer to the development of an adjuvant to mitigate cyclophosphamide-induced renal toxicity among patients treated with cyclophosphamide.