Biology Department, Faculty of Science, King Adulaziz University, Saudi Arabia.
Saudi J Biol Sci. 2010 Apr;17(2):105-14. doi: 10.1016/j.sjbs.2010.02.003. Epub 2010 Feb 24.
Taxol is a microtubule inhibitor drug widely used in treatment of many types of cancer. Nephrotoxicity is the most hazardous effect complicating chemotherapy in general and kidney functions must be monitored early during any chemotherapeutic course. The main objective of the present study was to investigate the effect of acute Taxol nephrotoxicity in mice. In the present study Taxol at different doses; MD, ID and MTD (0.6, 1.15 and 1.7 mg/kg), respectively, was given by intra-peritoneal route to 54 adult male mice with an average body weight of 20-25 g. Kidney samples was taken 6, 24, 48 h following administration, fixed in 10% neutral buffered formalin, paraffin sections 5 μm thick were stained by haematoxylin and eosin and PAS and then examined for histological changes. Samples from animals treated by the maximum dose (MTD = 1.7 mg/kg) for 48 h were fixed in 3% gluteraldehyde in phosphate buffer (pH 7.4) and processed for transmission electron microscope. Taxol given for short duration was found to produce marked degenerative changes in kidney parenchyma even in minimum tolerated dose (MD = 0.6 mg/kg). Individual variations were observed regarding the degree of nephrotoxicity. There was marked loss of renal tubules epithelial lining, damage of brush border and formation of hyaline casts within the damaged tubules. The alterations were in the form of both necrotic and apoptotic changes in the kidney tubules. Focal atrophy of glomerular tufts was also observed. Vascular congestion and degenerative changes in renal blood vessels were occasionally evident in some samples. Ultrastructure study revealed damage of glomerular membrane. Proximal tubule showed loss of basal infoldings, damage of brush border, mitochondrial degeneration and nuclear changes. Distal tubules also showed demarked degenerative changes. Increased frequency of micronuclei proved that Taxol had genotoxic effects in mice bone marrow cells. In conclusion Taxol had nephrotoxic effect on mice kidney that must be considered during its use as a chemotherapeutic agent in human.
紫杉醇是一种广泛用于治疗多种癌症的微管抑制剂药物。肾毒性是最危险的副作用，会使化疗复杂化，因此在任何化疗过程中都必须早期监测肾功能。本研究的主要目的是研究紫杉醇急性肾毒性在小鼠中的作用。在本研究中，不同剂量的紫杉醇（MD、ID 和 MTD，分别为 0.6、1.15 和 1.7mg/kg）通过腹腔途径给予 54 只平均体重为 20-25g 的成年雄性小鼠。给药后 6、24、48 小时采集肾脏样本，用 10%中性缓冲福尔马林固定，5μm 厚的石蜡切片用苏木精和伊红及 PAS 染色，然后检查组织学变化。用最大剂量（MTD=1.7mg/kg）处理 48 小时的动物样本用 3%戊二醛磷酸盐缓冲液（pH7.4）固定，并进行透射电镜处理。研究发现，紫杉醇短期给药即使在最低耐受剂量（MD=0.6mg/kg）下也会导致肾脏实质产生明显的退行性变化。个体之间的肾毒性程度存在差异。肾小管上皮衬里明显丧失，刷状缘受损，受损肾小管内形成透明管型。这些变化在肾小管中表现为坏死和凋亡改变。肾小球绒毛也出现局灶性萎缩。偶尔在一些样本中可见肾血管充血和退行性改变。超微结构研究显示肾小球膜受损。近端小管基底内陷丧失，刷状缘受损，线粒体变性和核改变。远端小管也显示出明显的退行性变化。微核频率增加证明紫杉醇对小鼠骨髓细胞具有遗传毒性作用。总之，紫杉醇对小鼠肾脏有肾毒性作用，在将其作为化疗药物用于人类时必须考虑到这一点。
