Gaedeke J, Fels L M, Bokemeyer C, Mengs U, Stolte H, Lentzen H
Division of Nephrology, Medical School Hannover, Germany.
Nephrol Dial Transplant. 1996 Jan;11(1):55-62.
The anticancer drug cisplatin is know to have toxic side-effects on different segments of the nephron. The flavonoid silibinin has previously been shown to be protective in models of hepatotoxicity. The aim of the present study was to evaluate, whether silibinin can also ameliorate alterations in renal glomerular and tubular function and tubular morphology induced by cisplatin.
In a rat model renal damage was induced by a single injection of cisplatin (5 mg/kg body weight). The protective effects of silibinin were studied in rats that received the flavonoid (200 mg/kg body weight, i.v.) 1 h prior to the administration of cisplatin. Kidney function was monitored by analysing urinary markers of glomerular and tubular function over a period of 11 days. Animals of a second group, with identical treatment, were sacrificed 4 days after drug application for an evaluation of tubular morphology at the light-microscopical level.
Administration of cisplatin caused a decline in kidney function within a day following treatment. Symptoms observed were for example decreases in creatinine clearance and increases in proteinuria, in the urinary activity of the proximal tubular enzymes alanine aminopeptidase and N-acetyl-beta-D-glucosaminidase and in renal magnesium wasting. The effects of cisplatin on creatinine clearance and proteinuria were totally prevented by a pretreatment of the animals with silibinin. Impairment of proximal tubular function was ameliorated, that is enzymuria and magnesium wasting was less pronounced. Silibinin alone had no effect on kidney function. Treatment with silibinin distinctly diminished morphological alterations observed in the S3-segment of the proximal tubule 4 days after cisplatin administration.
The effects of cisplatin on glomerular and proximal tubular function as well as proximal tubular morphology could totally or partly be ameliorated by silibinin. It is concluded the silibinin can act as a nephroprotectant and it is suggested that it could have beneficial effects on the kidney in clinical settings.
抗癌药物顺铂已知对肾单位的不同节段具有毒副作用。黄酮类化合物水飞蓟宾先前已被证明在肝毒性模型中具有保护作用。本研究的目的是评估水飞蓟宾是否也能改善顺铂诱导的肾小球和肾小管功能及肾小管形态的改变。
在大鼠模型中，通过单次注射顺铂（5mg/kg体重）诱导肾损伤。在给予顺铂前1小时，对接受黄酮类化合物（200mg/kg体重，静脉注射）的大鼠研究水飞蓟宾的保护作用。在11天的时间内，通过分析肾小球和肾小管功能的尿标志物来监测肾功能。对第二组接受相同治疗的动物，在给药4天后处死，以在光学显微镜水平评估肾小管形态。
顺铂给药后一天内导致肾功能下降。观察到的症状例如肌酐清除率降低、蛋白尿增加、近端肾小管酶丙氨酸氨基肽酶和N-乙酰-β-D-氨基葡萄糖苷酶的尿活性增加以及肾镁流失。用水飞蓟宾对动物进行预处理可完全预防顺铂对肌酐清除率和蛋白尿的影响。近端肾小管功能的损害得到改善，即酶尿和镁流失不那么明显。单独使用水飞蓟宾对肾功能没有影响。水飞蓟宾治疗明显减少了顺铂给药4天后在近端小管S3段观察到的形态学改变。
水飞蓟宾可完全或部分改善顺铂对肾小球和近端肾小管功能以及近端肾小管形态的影响。得出结论，水飞蓟宾可作为一种肾保护剂，并且表明它在临床环境中可能对肾脏有有益作用。
