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左旋肉碱和抗坏血酸联合给药可改善顺铂诱导的大鼠肾毒性。

Combined Administration of l-Carnitine and Ascorbic Acid Ameliorates Cisplatin-Induced Nephrotoxicity in Rats.

机构信息

a Department of Physiological Sciences , Faculty of Basic Medical Sciences, Obafemi Awolowo University , Ile-Ife , Osun State , Nigeria.

b Department of Haematology and Blood Transfusion , College of Medicine, Faculty of Basic Medical Sciences, Afe Babalola University , Ado Ekiti , Ekiti, State , Nigeria.

出版信息

J Am Coll Nutr. 2018 Jul;37(5):387-398. doi: 10.1080/07315724.2017.1409139. Epub 2018 Feb 9.

DOI:10.1080/07315724.2017.1409139
PMID:29425480
Abstract

OBJECTIVES

Cisplatin (CIS) is an effective antitumor drug. However, its clinical use is limited due to nephrotoxicity. l-Carnitine and vitamin C are both natural antioxidant that can be obtained from diets. This study investigated the effects of l-carnitine and/or vitamin C in rats against cisplatin-induced nephrotoxicity.

METHODS

Twenty-five male Wistar rats were divided into 5 groups of 5 rats each. Group 1, normal control. Group 2, positive control, received cisplatin (10 mg/kg/day intraperitoneally [i.p.]) for 3 days. Groups 3, 4, and 5 received cisplatin for 3 days and thereafter l-carnitine (50 mg/kg/day), vitamin C (100 mg/kg/day), or their combination, respectively, for 28 days. At the end of the study, a biochemical study was carried out in which nephrotoxicity markers, electrolytes, hematological indices, oxidative stress biomarkers, and renal histopathological alterations were evaluated.

RESULTS

CIS-treated rats developed significant polyuria, increase in the plasma levels of creatinine, urea, and inorganic phosphate (P), alteration in hematological parameters, and decrease in plasma levels of Na, Cl, K, Ca, and Mg. Measurements of 24-hour urine output demonstrated markedly decreased creatinine and urea and increased Na, Cl, K, Ca, and Mg levels in the CIS-treated group, whereas P levels were not changed. It also caused significantly decreased catalase (CAT), superoxide dismutase (SOD), and reduced glutathione (GSH) levels in the rats' kidneys. Histopathological scores revealed renal tubular damage in CIS-treated rats. However, l-carnitine, vitamin C, or their combination significantly attenuated the alterations caused by CIS in the plasma and kidneys of the rats.

CONCLUSION

l-Carnitine and vitamin C administration ameliorated CIS-induced nephrotoxicity due to their antioxidant and anti-inflammatory effects.

摘要

目的

顺铂(CIS)是一种有效的抗肿瘤药物。然而,由于其肾毒性,其临床应用受到限制。左旋肉碱和维生素 C 都是可从饮食中获得的天然抗氧化剂。本研究探讨了左旋肉碱和/或维生素 C 对顺铂诱导的肾毒性的影响。

方法

将 25 只雄性 Wistar 大鼠分为 5 组,每组 5 只。第 1 组为正常对照组。第 2 组为阳性对照组,腹腔内(i.p.)注射顺铂(10mg/kg/天)连续 3 天。第 3、4 和 5 组连续 3 天注射顺铂,然后分别给予左旋肉碱(50mg/kg/天)、维生素 C(100mg/kg/天)或两者联合治疗 28 天。研究结束时,进行生化研究,评估肾毒性标志物、电解质、血液学指标、氧化应激生物标志物和肾脏组织病理学改变。

结果

CIS 处理的大鼠出现多尿、血浆肌酐、尿素和无机磷(P)水平升高、血液学参数改变以及血浆 Na、Cl、K、Ca 和 Mg 水平降低。24 小时尿排量测量显示 CIS 处理组大鼠的肌酐和尿素水平明显降低,Na、Cl、K、Ca 和 Mg 水平升高,而 P 水平未改变。它还导致大鼠肾脏中的过氧化氢酶(CAT)、超氧化物歧化酶(SOD)和还原型谷胱甘肽(GSH)水平显著降低。组织病理学评分显示 CIS 处理的大鼠存在肾小管损伤。然而,左旋肉碱、维生素 C 或两者联合使用可显著减轻 CIS 对大鼠血浆和肾脏的影响。

结论

左旋肉碱和维生素 C 的给药可通过其抗氧化和抗炎作用改善 CIS 诱导的肾毒性。

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