Cyclophosphamide (CP) is one of the famous anti-cancer drugs. However, CP-induced hepatotoxicity is a dose-limiting side effect. The present study aimed to investigate the potential protective effect of geraniol (GOH), the main ingredient of Palmarosa oil and rose oil, against CP-induced hepatotoxicity in rats. Results showed that CP provoked a marked elevation in serum levels of alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase. In addition, oxidative stress was significantly boosted in CP-treated rats as compared to control rats. On the other hand, GOH (200 mg/kg, p.o.) administration attenuated CP-evoked disturbances in the above-mentioned parameters. Moreover, histopathological aberrations in CP-treated rats were significantly ameliorated in GOH-treated rats. GOH markedly abrogated CP-induced inflammation via decreasing the protein expression of nuclear factor-kappa B, inducible nitric oxide synthase and cyclo-oxygenase 2, as well as reducing the levels of pro-inflammatory cytokines in CP-treated rats. CP induced activation of MAPK; p38 and JNK and diminished PPAR-γ protein expression. GOH effectively reversed all these effects. In conclusion, GOH is suggested to be a potential candidate for attenuation of CP-induced hepatotoxicity. This effect is attributed to its antioxidant and anti-inflammatory activities, as well as, modulation of MAPK and PPAR-γ signaling pathways.

中文翻译：

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香叶醇可预防环磷酰胺诱导的大鼠肝毒性：MAPK和PPAR-γ信号通路的可能作用。

环磷酰胺（CP）是著名的抗癌药物之一。但是，CP诱导的肝毒性是剂量限制的副作用。本研究旨在研究香叶醇（GOH）（棕榈油和玫瑰油的主要成分）对CP诱导的大鼠肝毒性的潜在保护作用。结果表明，CP引起血清丙氨酸转氨酶，天冬氨酸转氨酶和碱性磷酸酶水平的显着升高。此外，与对照组相比，经CP处理的大鼠氧化应激显着增强。另一方面，GOH（200 mg / kg，口服）给药可减轻上述参数中CP引起的干扰。此外，CP-处理的大鼠中的组织病理学异常在GOH-处理的大鼠中显着改善。GOH通过减少核因子-κB，诱导型一氧化氮合酶和环加氧酶2的蛋白质表达，以及减少经CP治疗的大鼠中促炎细胞因子的水平，显着消除了CP诱导的炎症。CP诱导MAPK激活；p38和JNK并降低PPAR-γ蛋白表达。GOH有效地扭转了所有这些影响。总之，建议GOH是减轻CP诱导的肝毒性的潜在候选者。该作用归因于其抗氧化剂和抗炎活性，以及​​对MAPK和PPAR-γ信号通路的调节。p38和JNK并降低PPAR-γ蛋白表达。GOH有效地扭转了所有这些影响。总之，建议GOH是减轻CP诱导的肝毒性的潜在候选者。该作用归因于其抗氧化和抗炎活性，以及​​对MAPK和PPAR-γ信号通路的调节。p38和JNK并降低PPAR-γ蛋白表达。GOH有效地扭转了所有这些影响。总之，建议GOH是减轻CP诱导的肝毒性的潜在候选者。该作用归因于其抗氧化和抗炎活性，以及​​对MAPK和PPAR-γ信号通路的调节。