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水飞蓟素改善顺铂诱导的大鼠肝毒性:组织病理学和超微结构研究。

Silymarin ameliorates cisplatin-induced hepatotoxicity in rats: histopathological and ultrastructural studies.

作者信息

Abdelmeguid N E, Chmaisse H N, Abou Zeinab N S

机构信息

Department of Zoology, Faculty of Science, Alexandria University, Moharram Bey, Alexandria 2151, Egypt.

出版信息

Pak J Biol Sci. 2010 May 15;13(10):463-79. doi: 10.3923/pjbs.2010.463.479.

DOI:10.3923/pjbs.2010.463.479
PMID:21848071
Abstract

The benefit of silymarin, a plant extract with strong antioxidant activity against hepatotoxicity induced by cisplatin in rats was investigated in this study. Cisplatin is one of the most effective chemotherapeutic drugs, yet it alone does not achieve a satisfactory therapeutic outcome and at high doses it can produce undesirable side effects. Five equal-sized groups (18 rats each) of male Sprague Dawley rats [control, vehicle; cisplatin; silymarin 2 h after cisplatin injection; and silymarin 2 h before cisplatin injection] were used. Histopathological and ultrastructural observation of livers were carried out using light and electron microscopy. Results documented that cisplatin produced behavioral, external features animal changes, as well as hazard pathological picture changes in liver where most hepatocytes appeared diminutive with vacuolated cytoplasm, sinusoids dilated and organelle disorganized. These results revealed that cisplatin may be toxic and terminates in complex liver damage. Administrations of silymarin 2 h after cisplatin, significantly increase the body weight returning it to normal, yet it failed in complete protection against the pathological alteration caused by cisplatin. Pretreatment with silymarin 2 h before cisplatin significantly decreased the pathological changes induced by cisplatin and appeared highly protective. These results suggested that silymarin possess protective effects against cisplatin hepatotoxic action in animal models. Since, no significant toxicity of silymarin is reported in human studies, this plant extract can be used as a dietary supplement by patients taking anticancerous medications and might serve as a novel combination agent with cisplatin since it plays a significant role in reducing its toxicity.

摘要

本研究调查了水飞蓟素(一种对大鼠顺铂诱导的肝毒性具有强大抗氧化活性的植物提取物)的益处。顺铂是最有效的化疗药物之一,但单独使用时治疗效果并不理想,且高剂量使用会产生不良副作用。本研究使用了五组大小相等的雄性斯普拉格 - 道利大鼠(每组18只),分别为[对照组、赋形剂组;顺铂组;顺铂注射后2小时给予水飞蓟素组;顺铂注射前2小时给予水飞蓟素组]。使用光学显微镜和电子显微镜对肝脏进行组织病理学和超微结构观察。结果表明,顺铂导致了行为、动物外观特征的变化,以及肝脏出现有害的病理图像变化,其中大多数肝细胞体积变小,细胞质空泡化,肝血窦扩张,细胞器紊乱。这些结果表明顺铂可能具有毒性,并最终导致复杂的肝脏损伤。顺铂注射后2小时给予水飞蓟素,可显著增加体重使其恢复正常,但未能完全防止顺铂引起的病理改变。顺铂注射前2小时用水飞蓟素预处理可显著降低顺铂诱导的病理变化,显示出高度的保护作用。这些结果表明水飞蓟素对动物模型中顺铂的肝毒性作用具有保护作用。由于在人体研究中未报告水飞蓟素具有明显毒性,这种植物提取物可被服用抗癌药物的患者用作膳食补充剂,并且由于它在降低顺铂毒性方面发挥了重要作用,可能作为与顺铂联合使用的新型药物。

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