Department of Pharmacology and Therapeutics, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia.
Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia.
Pharm Biol. 2023 Dec;61(1):298-305. doi: 10.1080/13880209.2023.2166965.
CONTEXT: Cisplatin, as a first-line treatment for ovarian cancer, is associated with debilitating adverse effects, including nephrotoxic and haematotoxic effects. OBJECTIVE: This study determines whether nanocurcumin, combined with cisplatin, would give additional benefit to kidney function and haematological parameters in rats with ovarian cancer. MATERIALS AND METHODS: Twenty-five Wistar rats were divided into five untreated rats and 20-dimethylbenz()anthracene (DMBA)-induced ovarian cancer rats. The 20 ovarian cancer rats were divided into four treatment groups: vehicle, cisplatin, cisplatin-curcumin, and cisplatin-nanocurcumin. Cisplatin was given at the dose of 4 mg/kg BW once weekly, while curcumin or nanocurcumin was administered at 100 mg/kg BW daily for four weeks. At the end of treatment, we analysed kidney function, haematological parameters, and inflammatory and oxidative stress markers from plasma. RESULTS: Nanocurcumin alleviates the increase in kidney function markers and abnormalities in haematological indices in rats treated with cisplatin. Compared to cisplatin-treated rats, plasma urea levels decreased from 66.4 to 47.7 mg/dL, creatinine levels lowered from 0.87 to 0.82 mg/dL, and neutrophil gelatinase-associated lipocalin (NGAL) levels declined from 8.51 to 3.59 mIU/mg protein. Furthermore, the therapy increased glutathione activities (from 2.02 to 3.23 U/µL), reduced lipid peroxidation (from 0.54 to 0.45 nmol/mL), and decreased plasma TNF-α (from 270.6 to 217.8 pg/mL). CONCLUSIONS: Cisplatin with nanocurcumin in an ovarian cancer rat model may provide additional benefits as a preventive agent against renal impairment and cisplatin-induced haematological toxicity. However, further research is required to prove that using nanocurcumin for a more extended time would not affect its anticancer properties.
背景:顺铂作为卵巢癌的一线治疗药物,会引起使人虚弱的不良反应,包括肾毒性和血液毒性。 目的:本研究旨在确定姜黄素纳米粒与顺铂联合应用是否能为卵巢癌大鼠的肾功能和血液学参数带来额外益处。 材料和方法:将 25 只 Wistar 大鼠分为 5 只未处理的大鼠和 20 只二甲基苯并蒽(DMBA)诱导的卵巢癌大鼠。20 只卵巢癌大鼠分为 4 个治疗组:对照组、顺铂组、顺铂-姜黄素组和顺铂-纳米姜黄素组。顺铂每周按 4mg/kgBW 给予一次,而姜黄素或纳米姜黄素按 100mg/kgBW 每日给予,持续 4 周。治疗结束时,我们分析了血浆中的肾功能、血液学参数、炎症和氧化应激标志物。 结果:纳米姜黄素减轻了顺铂治疗大鼠肾功能标志物的增加和血液学指标的异常。与顺铂治疗组大鼠相比,血浆尿素水平从 66.4mg/dL 降至 47.7mg/dL,肌酐水平从 0.87mg/dL 降至 0.82mg/dL,中性粒细胞明胶酶相关脂质运载蛋白(NGAL)水平从 8.51mIU/mg 蛋白降至 3.59mIU/mg 蛋白。此外,该疗法还增加了谷胱甘肽的活性(从 2.02U/µL 增加至 3.23U/µL),降低了脂质过氧化(从 0.54nmol/mL 降至 0.45nmol/mL),并降低了血浆 TNF-α(从 270.6pg/mL 降至 217.8pg/mL)。 结论:顺铂联合卵巢癌大鼠模型中的纳米姜黄素可能作为预防肾损伤和顺铂引起的血液毒性的辅助药物提供额外益处。然而,需要进一步的研究来证明使用纳米姜黄素更长时间不会影响其抗癌特性。
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