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13 周后,暴露于虫草与其宿主蚕蛹复合物下的大鼠的肾脏损伤生物标志物的变化。

Change in kidney damage biomarkers after 13 weeks of exposing rats to the complex of Paecilomyces sinclairii and its host Bombyx mori larvae.

机构信息

Agro-Material Safety Evaluating Division, National Academy of Agricultural Science, Rural Development Administration, Suwon 441-707, Republic of Korea.

出版信息

Food Chem Toxicol. 2013 Sep;59:177-86. doi: 10.1016/j.fct.2013.05.041. Epub 2013 Jun 6.

DOI:10.1016/j.fct.2013.05.041
PMID:23747716
Abstract

Complex of Paecilomyces sinclairii and host larvae, Bombyx mori, is a well known health food; however, concerns about nephrotoxicity have been raised. Kidney toxicity was investigated after 13 weeks of administering the complex orally to rats with parameters including blood urea nitrogen (BUN), creatinine, and kidney damage biomarkers, beta-2-microglobulin (β2m), glutathione S-transferase alpha (GST-α), kidney injury molecule 1 (KIM-1), tissue inhibitor of matrix metalloproteinase 1 (TIMP-1), vascular endothelial growth factor (VEGF), calbindin, clusterin, cystatin C, neutrophil gelatinase-associated lipocalin (NGAL), and osteopontin. Dose-dependent kidney cell karyomegaly and tubular hypertrophy were observed, with higher severity in males. There was a dose-dependent increase in KIM-1 and TIMP-1 levels in kidney and urinary KIM-1, cystatin C, β2m, and osteopontin levels. KIM-1 and TIMP-1 increased in male kidneys had not recovered by 2 weeks after stopping exposure. Cystatin C in kidney was significantly lowered in all treatment groups at 13 weeks of administration. All the changes were more noticeable in males. These data indicate that the complex damage renal tubule cells with histopathological lesions and changes in biomarker levels. Kidney and urinary KIM-1 and cystatin C were the most markedly affected and early increased indicators among biomarkers tested, whereas BUN and creatinine were not affected.

摘要

蛹虫草复合宿主幼虫(家蚕)是一种广为人知的保健品,但人们对其肾毒性表示担忧。本研究通过给大鼠灌胃该复合物 13 周,观察了其对大鼠的肾毒性,检测了血尿素氮(BUN)、肌酐、肾损伤生物标志物β2-微球蛋白(β2m)、谷胱甘肽 S-转移酶α(GST-α)、肾损伤分子 1(KIM-1)、组织抑制剂金属蛋白酶 1(TIMP-1)、血管内皮生长因子(VEGF)、钙结合蛋白、簇蛋白、胱抑素 C、中性粒细胞明胶酶相关脂质运载蛋白(NGAL)和骨桥蛋白等参数的变化。结果发现,复合物可导致大鼠肾细胞出现剂量依赖性的巨细胞和肾小管肥大,且雄性大鼠的病变程度更严重。复合物还可导致肾和尿 KIM-1、胱抑素 C、β2m 和骨桥蛋白水平呈剂量依赖性升高,并且雄性大鼠肾组织中的 KIM-1 和 TIMP-1 水平升高,在停止暴露后 2 周仍未恢复正常。复合物给药 13 周后,大鼠肾组织中胱抑素 C 水平显著降低,且所有处理组的变化在雄性大鼠中更为明显。这些数据表明,该复合物可导致肾组织出现病理损伤和生物标志物水平变化,从而损害肾小管细胞。肾和尿 KIM-1 和胱抑素 C 是受影响最明显和最早升高的生物标志物,而 BUN 和肌酐不受影响。

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