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评价乙酰左旋肉碱对实验性顺铂肾毒性的影响。

Evaluation of the effect of acetyl L-carnitine on experimental cisplatin nephrotoxicity.

机构信息

Departments of Pediatrics, Dokuz Eylul University Faculty of Medicine, Izmir, Turkey.

出版信息

Chemotherapy. 2009;55(6):451-9. doi: 10.1159/000240020. Epub 2009 Dec 8.

DOI:10.1159/000240020
PMID:19996591
Abstract

BACKGROUND/AIMS: To evaluate the protective effects of acetyl L-carnitine (ALCAR) on cisplatin-induced nephrotoxicity in rats, and to gain insights into the possible protective mechanisms of ALCAR against nephrotoxicity.

METHODS

Twenty-eight Wistar rats were divided into four groups. Group 1 was administered saline only, group 2 was administered ALCAR, group 3 was administered cisplatin, and group 4 was administered ALCAR prior to cisplatin. Rats were sacrificed after 72 h of cisplatin/saline infusion. Serum creatinine and glomerular filtration rate values were obtained, and kidney samples were examined by light and electron microscopy. Apoptotic cell death and caspase-3, 8 and 9 activities were studied immunohistochemically.

RESULTS

In group 4, ALCAR administration resulted in an improvement in kidney function tests. Histopathological findings confirmed the biochemical data. Whilst the fusion of the foot processes of podocytes was observed in group 3, they were intact in group 4 on electron-microscopic examination. Apoptotic cell death and caspase-3, 8 and 9 activities were also decreased in group 4 compared to group 3.

CONCLUSIONS

Antioxidative, antiapoptotic and anti-inflammatory properties of ALCAR were supported by the findings that this agent improves kidney function tests and has the effects of tissue protection and inhibition of apoptosis in cisplatin-induced nephrotoxicity.

摘要

背景/目的:评估乙酰左旋肉碱 (ALCAR) 对顺铂诱导的大鼠肾毒性的保护作用,并深入了解 ALCAR 对肾毒性的可能保护机制。

方法

将 28 只 Wistar 大鼠分为四组。第 1 组仅给予生理盐水,第 2 组给予 ALCAR,第 3 组给予顺铂,第 4 组给予 ALCAR 后给予顺铂。顺铂/生理盐水输注 72 小时后处死大鼠。测定血清肌酐和肾小球滤过率值,并通过光镜和电镜检查肾组织。免疫组化研究细胞凋亡和 caspase-3、8 和 9 的活性。

结果

第 4 组给予 ALCAR 可改善肾功能检查结果。组织病理学发现证实了生化数据。虽然在第 3 组中观察到足细胞的足突融合,但在第 4 组中在电镜下它们是完整的。与第 3 组相比,第 4 组的细胞凋亡和 caspase-3、8 和 9 活性也降低。

结论

ALCAR 的抗氧化、抗凋亡和抗炎特性得到支持,因为该药物改善了肾功能检查,并具有在顺铂诱导的肾毒性中保护组织和抑制细胞凋亡的作用。

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