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首页> 外文期刊>Saudi Journal of Biological Sciences >Acute Taxol nephrotoxicity: Histological and ultrastructural studies of mice kidney parenchyma
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Acute Taxol nephrotoxicity: Histological and ultrastructural studies of mice kidney parenchyma

机译：急性紫杉醇肾毒性：小鼠肾脏实质的组织学和超微结构研究

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摘要

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 1.7mg/kg), respectively, was given by intra-peritoneal route to 54 adult male mice with an average body weight of 20-25g. Kidney samples was taken 6, 24, 48h following administration, fixed in 10% neutral buffered formalin, paraffin sections 5@mm thick were stained by haematoxylin and eosin and PAS and then examined for histological changes. Samples from animals treated by the maximum dose (MTD=1.7mg/kg) for 48h 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=0.6mg/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.
机译：紫杉酚是一种微管抑制剂药物，广泛用于治疗多种类型的癌症。一般而言，肾毒性是使化疗复杂化的最危险的作用，在任何化疗过程中必须尽早监测肾功能。本研究的主要目的是研究小鼠急性紫杉醇肾毒性的作用。在本研究中，不同剂量的紫杉酚;通过腹膜内途径对54只平均体重为20-25g的成年雄性小鼠给予MD，ID和MTD（0.6、1.15和1.7mg / kg）。给药后第6、24、48小时取肾样品，固定在10％中性福尔马林缓冲液中，用苏木精，曙红和PAS对5mm厚的石蜡切片染色，然后检查组织学变化。用最大剂量（MTD = 1.7mg / kg）处理48小时的动物样品固定在磷酸盐缓冲液（pH 7.4）中的3％戊二醛中，并进行透射电子显微镜处理。即使在最小耐受剂量（MD = 0.6mg / kg）下，短时间给予紫杉醇也会使肾脏实质发生明显的退行性改变。观察到关于肾毒性的程度的个体差异。肾小管上皮内衬明显丧失，刷状缘受损，在受损小管内形成透明管。改变以肾小管中坏死和凋亡改变的形式出现。还观察到了肾小球簇的局灶性萎缩。在某些样本中偶尔会出现血管充血和肾血管的退行性变化。超微结构研究显示肾小球膜受损。近端肾小管显示基底皱褶消失，刷缘破坏，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，紫杉醇对小鼠肾脏具有肾毒性作用，在其作为人的化学治疗剂使用时必须加以考虑。

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