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甲磺酸去铁胺改善顺铂诱导的肾毒性作用的实验研究

Experimental study on effects of deferoxamine mesilate in ameliorating cisplatin-induced nephrotoxicity.

作者信息

Ozdemir E, Dokucu A I, Uzunlar A K, Ece A, Yaldiz M, Oztürk H

机构信息

Department of Urology, Dicle University Hospital, Diyarbakir, Turkey.

出版信息

Int Urol Nephrol. 2002;33(1):127-31. doi: 10.1023/a:1014442027991.

Abstract

PURPOSE

Cisplatin (CCDP), an indispensable agent of several chemotherapy protocols, has serious dose limiting side effects, including nephrotoxicity. In this experimental study, we used deferoxamine mesilate (DFO), an iron chelating agent, to ameliorate cisplatin-induced nephrotoxicity.

MATERIALS AND METHODS

Sixty adult male bulb-c mice were divided in 6 equal groups. Group 1 received distilled water, group 2 received 100 mg/kg DFO, group 3 received 0.9 mg/kg CCDP, group 4 received 100 mg/kg DFO one hour before 0.9 mg/kg CCDP, group 5 received 1.8 mg/kg CCDP, and group 6 received 200 mg/kg DFO one hour before 1.8 mg/kg CCDP transperitoneally for 10 days. The next day, blood and urine samples were obtained, and all the animals were sacrificed, the kidneys and testes were removed, and histopathologic and biochemical analyses were performed.

RESULTS

Low-dose and high-dose CCDP treated mice had significantly more extensive proximal tubular degeneration (p < 0.001) when compared to control animals. Moreover, these changes were significantly less extensive in the mice taking DFO than mice taking CCDP. DFO showed no effect on cisplatin induced testicular histopathology. The cisplatin administration significantly increased the serum urea and plasma creatinin concentrations, and DFO administration prior to CCDP significantly decreased serum urea and plasma creatinin concentrations.

CONCLUSION

Our findings suggest that DFO administration may be safe and useful for ameliorating cisplatin-induced nephrotoxicity.

摘要

目的

顺铂(CCDP)是多种化疗方案中不可或缺的药物,但具有严重的剂量限制性副作用,包括肾毒性。在本实验研究中,我们使用铁螯合剂去铁胺甲磺酸盐(DFO)来改善顺铂诱导的肾毒性。

材料与方法

将60只成年雄性球茎C小鼠平均分为6组。第1组接受蒸馏水,第2组接受100mg/kg DFO,第3组接受0.9mg/kg CCDP,第4组在接受0.9mg/kg CCDP前1小时接受100mg/kg DFO,第5组接受1.8mg/kg CCDP,第6组在接受1.8mg/kg CCDP前1小时经腹腔注射200mg/kg DFO,持续10天。次日,采集血液和尿液样本,处死所有动物,取出肾脏和睾丸,进行组织病理学和生化分析。

结果

与对照动物相比,低剂量和高剂量CCDP处理的小鼠近端肾小管变性明显更广泛(p<0.001)。此外,服用DFO的小鼠的这些变化比服用CCDP的小鼠明显更轻。DFO对顺铂诱导的睾丸组织病理学无影响。顺铂给药显著增加血清尿素和血浆肌酐浓度,而在CCDP之前给予DFO显著降低血清尿素和血浆肌酐浓度。

结论

我们的研究结果表明,给予DFO可能对改善顺铂诱导的肾毒性是安全有效的。

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