An Extract of Rhodobacter sphaeroides Reduces Cisplatin-Induced Nephrotoxicity in Mice

An Extract of Rhodobacter sphaeroides Reduces Cisplatin-Induced Nephrotoxicity in Mice
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DOI:
10.3390/toxins5122353
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发表时间:
2013-12-01
期刊:
影响因子:
4.2
通讯作者:
Lee, Che-Hsin
Lee, Che-Hsin
中科院分区:
医学2区
文献类型:
--
作者:
Chang, Wen-Wei;Liu, Jau-Jin;Lee, Che-Hsin

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顺铂用于治疗各种类型的实体瘤。肾损伤严重限制了顺铂的使用。肾细胞凋亡、氧化应激和炎症有助于顺铂诱导的肾毒性。在此之前,我们发现球形红杆菌(Rhodobacter sphaeroides, Lycogen)提取物可抑制葡聚糖硫酸钠(DSS)诱导结肠炎模型中活化巨噬细胞的促炎细胞因子和一氧化氮的产生。在这里,我们评估了Lycogen(一种有效的抗炎剂)在顺铂诱导的肾损伤小鼠中的作用。我们发现,由于肾细胞中caspase-3表达的减少,肾损伤的减轻与细胞凋亡的减少相关。口服lyco原可显著降低肾损伤小鼠肿瘤坏死因子-和白细胞介素-1的表达。糖原可减轻顺铂所致肾损伤小鼠的肾功能障碍。治疗的保护作用包括阻断顺铂引起的血清尿素氮和肌酐升高。同时,lyco原可以减轻肾损伤小鼠的体重损失,显著延长肾损伤小鼠的生存期。我们认为,lyco原具有抗炎活性,这是治疗顺铂所致肾损伤的一个有希望的策略。
Cisplatin is used as a treatment for various types of solid tumors. Renal injury severely limits the use of cisplatin. Renal cell apoptosis, oxidative stress, and inflammation contribute to cisplatin-induced nephrotoxicity. Previously, we found that an extract of Rhodobacter sphaeroides (Lycogen) inhibited proinflammatory cytokines and the production of nitric oxide in activated macrophages in a dextran sodium sulfate (DSS)-induced colitis model. Here, we evaluated the effect of Lycogen, a potent anti-inflammatory agent, in mice with cisplatin-induced renal injury. We found that attenuated renal injury correlated with decreased apoptosis due to a reduction in caspase-3 expression in renal cells. Oral administration of Lycogen significantly reduced the expression of tumor necrosis factor- and interleukin-1 in mice with renal injury. Lycogen reduces renal dysfunction in mice with cisplatin-induced renal injury. The protective effects of the treatment included blockage of the cisplatin-induced elevation in serum urea nitrogen and creatinine. Meanwhile, Lycogen attenuated body weight loss and significantly prolonged the survival of mice with renal injury. We propose that Lycogen exerts anti-inflammatory activities that represent a promising strategy for the treatment of cisplatin-induced renal injury.