Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil.
Neurotoxicology. 2013 Jan;34:205-11. doi: 10.1016/j.neuro.2012.09.011. Epub 2012 Oct 2.
The potential neuroprotective benefits of curcumin against cisplatin neurotoxicity were investigated. Curcumin is a polyphenol derived from the rhizome of Curcuma longa whose pharmacological effects include antioxidant, anti-inflammatory and anti-cancer properties. Cisplatin is a potent chemotherapeutic drug with activity against a wide variety of tumors, although it has notorious side effects. Cisplatin neurotoxicity is clinically evident in patients that have undergone a full course of chemotherapy and develop a peripheral neuropathy that may affect the treatment regimen and the patient's qualify of life. In this study, we examined whether curcumin can protect against cisplatin neurite outgrowth inhibition in PC12 cells, which is an indicator of the protective potential against neuropathy. We also investigated whether curcumin affects cisplatin effectiveness by analyzing the modulation of p53 gene expression and its effect on cisplatin cytotoxicity in HepG2 tumor cells. Non-cytotoxic concentrations of curcumin reduced in vitro neurotoxicity of cisplatin in PC12 cells. The treatment of PC12 cells with cisplatin (10μg/mL) significantly reduced neurite outgrowth. The tested concentration of curcumin (1.0 and 10μg/mL) did not result in neurite toxicity but nevertheless diminished cisplatin-induced inhibition of neurite outgrowth by up to 50% (p<0.05). Our results indicate that curcumin does not compromise cisplatin's anticancer activity. Curcumin neither suppressed p53 mRNA transcription nor protected tumor cells against cisplatin cytotoxicity. These results indicate that curcumin may reduce cisplatin-induced neurotoxicity, and clinical studies should potentially be considered.
研究了姜黄素对顺铂神经毒性的潜在神经保护作用。姜黄素是从姜黄根茎中提取的多酚，其药理作用包括抗氧化、抗炎和抗癌特性。顺铂是一种有效的化疗药物，对多种肿瘤具有活性，尽管它有明显的副作用。顺铂神经毒性在接受全疗程化疗的患者中临床明显，会导致周围神经病，可能影响治疗方案和患者的生活质量。在这项研究中，我们研究了姜黄素是否可以防止 PC12 细胞中的顺铂神经突起生长抑制，这是对神经病变保护潜力的指标。我们还通过分析 p53 基因表达的调节及其对 HepG2 肿瘤细胞中顺铂细胞毒性的影响，研究了姜黄素对顺铂疗效的影响。非细胞毒性浓度的姜黄素降低了 PC12 细胞中顺铂的体外神经毒性。用顺铂（10μg/ml）处理 PC12 细胞显著降低了神经突起的生长。测试浓度的姜黄素（1.0 和 10μg/ml）本身不会导致神经突起毒性，但仍能使顺铂诱导的神经突起生长抑制减少多达 50%（p<0.05）。我们的结果表明，姜黄素不会损害顺铂的抗癌活性。姜黄素既不抑制 p53 mRNA 转录，也不保护肿瘤细胞免受顺铂细胞毒性。这些结果表明，姜黄素可能减轻顺铂引起的神经毒性，应考虑进行临床研究。
