Renoprotective Effects of Fermented Black Ginseng through Ameliorating Oxidative Stress Associated with Cisplatin-Induced Acute Nephrotoxicity in Mice

S. Roh, O. Kwon, Young-bae Seo
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Abstract

We aimed to evaluate the renal protective capacity of Fermented Black Ginseng (FBG) and its mechanism to reduce the cisplatin-induced nephrotoxicity. Nephrotoxicity was induced by a single intraperitoneal injection of cisplatin (20 mg/kg) and treated with white ginseng (WB) and FBG (200 mg/kg/day, orally) for 4 days before cisplatin treatment. Biochemical results showed that WG and FBG pretreatment significantly reduced the increase of blood urea nitrogen (BUN) and creatinine, and histopathological changes were meaningfully ameliorated. Cisplatin increased the production of reactive oxygen species (ROS) and depletion of Glutathione (GSH) in serum and kidney, whereas, WG or FBG administration markedly down-regulated. Moreover, the expression of nuclear factor-kappaB (NF-κB), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), tumor necrosis factor-α (TNF-α), and interleukin (IL)-6 was markedly suppressed by both WB and FBG. However, FBG pretreatment was more effective than those of WG in COX-2, iNOS, and IL-6 levels. Moreover, FBG treated mice significantly up-regulated the antioxidative enzymes. In HPLC analysis, the increasing ginsenoside contents that include Rg1, Re, Rb1, Rc, Rb3, Rd, Rg3, Rk1, and Rg5 by heat-processing were greater about 5.7 fold when fermentation additionally. Taken together, FBG may be a worthful candidate for the prevention of nephrotoxicity in patients receiving cisplatin.
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发酵黑参改善氧化应激对小鼠顺铂急性肾毒性的保护作用
本研究旨在探讨发酵黑参(FBG)对肾脏的保护作用及其降低顺铂肾毒性的机制。顺铂治疗前4天单次腹腔注射顺铂(20 mg/kg),并用白参(WB)和FBG (200 mg/kg/天,口服)治疗。生化结果显示,WG和FBG预处理显著降低了血尿素氮(BUN)和肌酐的升高,组织病理学改变有明显改善。顺铂增加了血清和肾脏中活性氧(ROS)的产生和谷胱甘肽(GSH)的消耗,而WG或FBG则明显下调。此外,WB和FBG显著抑制了核因子κ b (NF-κB)、环氧化酶-2 (COX-2)、诱导型一氧化氮合酶(iNOS)、肿瘤坏死因子-α (TNF-α)和白细胞介素-6的表达。但在COX-2、iNOS和IL-6水平上,FBG预处理比WG预处理更有效。此外,FBG处理小鼠的抗氧化酶显著上调。HPLC分析表明,经热处理后人参皂苷Rg1、Re、Rb1、Rc、Rb3、Rd、Rg3、Rk1、Rg5含量增加约5.7倍。综上所述,FBG可能是预防顺铂患者肾毒性的一个有价值的候选物。
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