Zhang Y, Wang Q, Wang Y-D, Sun B, Leng X-W, Li Q, Ren L-Q
1 Department of Experimental Pharmacology and Toxicology, School of Pharmacy, Jilin University, Changchun, Jilin Province, China.
2 Cancer Center, The First Hospital of Jilin University, Changchun, Jilin Province, China.
Hum Exp Toxicol. 2019 Jan;38(1):118-128. doi: 10.1177/0960327118785233. Epub 2018 Jul 2.
Cisplatin (CP) is one of the most effective and widely used compounds in the treatment of disease, including cancer, but is known to induce toxicity in patients. Rutin (RUT) is a flavonoid glycoside from Sophora japonica L. that has been shown to possess antioxidative, anti-inflammatory, and antiviral properties. RUT is also known to attenuate cardiotoxicity, isoproterenol-induced cardiac fibrosis, and ischemia/reperfusion-associated hemodynamic alteration, and prevents high glucose-induced renal glomerular endothelial hyperpermeability. In this study, we investigated the effect of RUT on CP-induced nephrotoxicity. CP was used to induce toxicity in human mesangial cells (HMCs), HMCs were pretreated with different concentrations of RUT before being exposed to 10 μg/mL of CP. A positive group was pretreated with antioxidant agent N-acetylcysteine prior to CP administration. At doses between 12.5 and 25 μM, RUT prevented CP-induced reduction in cell viability. Treatment with RUT suppressed intracellular reactive oxygen species and malonic dialdehyde levels and inhibited cell apoptosis. RUT reversed the CP-induced upregulation of p53, cleaved-caspase-3, and increased pro-caspase-3 and pro-caspase-9 levels. In conclusion, the RUT can relieve CP-induced nephrotoxicity by inhibiting the p53/caspase signaling pathway.
顺铂（CP）是治疗包括癌症在内的疾病最有效且应用最广泛的化合物之一，但已知会在患者中诱发毒性。芦丁（RUT）是一种来自槐树的黄酮苷，已被证明具有抗氧化、抗炎和抗病毒特性。还已知RUT可减轻心脏毒性、异丙肾上腺素诱导的心脏纤维化以及缺血/再灌注相关的血流动力学改变，并预防高糖诱导的肾小球内皮细胞高通透性。在本研究中，我们研究了RUT对CP诱导的肾毒性的影响。用CP诱导人系膜细胞（HMCs）产生毒性，在暴露于10μg/mL CP之前，用不同浓度的RUT预处理HMCs。阳性组在给予CP之前用抗氧化剂N-乙酰半胱氨酸预处理。在12.5至25μM的剂量下，RUT可防止CP诱导的细胞活力降低。RUT处理可抑制细胞内活性氧和丙二醛水平，并抑制细胞凋亡。RUT逆转了CP诱导的p53、裂解的半胱天冬酶-3上调，并增加了前半胱天冬酶-3和前半胱天冬酶-9水平。总之，RUT可通过抑制p53/半胱天冬酶信号通路减轻CP诱导的肾毒性。
