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膳食脂肪改变了大鼠体内甲基汞的肾毒性特征。

Dietary fats altered nephrotoxicity profile of methylmercury in rats.

作者信息

Jin Xiaolei, Lok Eric, Caldwell Don, Mueller Rudi, Kapal Kamla, Liston Virginia, Kubow Stan, Chan Hing Man, Mehta Rekha

机构信息

Toxicology Research Division, Food Directorate, HPFB, Health Canada, Ottawa, Ontario K1A0L2, Canada.

出版信息

J Appl Toxicol. 2009 Mar;29(2):126-40. doi: 10.1002/jat.1389.

Abstract

Weanling male Sprague-Dawley rats were administered semi-purified isocaloric diet containing soy oil (SO), seal oil (SE), docosahexaenoic acid (DHA), fish oil (FO) or lard (LA) for 28 days, and then gavaged with 0, 1 or 3 mg MeHg kg(-1) body weight per day and fed the same diet for 14 days. Serum and 24 h urine samples were collected on the day of necropsy, and analyzed for markers of kidney function and diseases. Kidney slices were analyzed for para-amino-hippurate (PAH) and tetraethylammonium (TEA) uptake, total mercury and MeHg content, and examined for pathological lesions. Total mercury and MeHg contents increased significantly and dose-dependently in all dietary groups. MeHg significantly increased relative kidney weight in all groups, serum creatinine in all except SO group, serum uric acid in the DHA and LA groups, serum Mg in all except the LA group, and urinary protein in the SO group. MeHg significantly decreased serum urea nitrogen in SE, FO and LA groups, urinary creatinine in the DHA group, PAH uptake in all except the SE group, and TEA uptake in all groups. MeHg caused nephrosis in all dietary groups. MeHg also significantly increased neutrophil counts in all except the SE group, decreased serum albumin and triglyceride in all except the DHA group, and increased serum total cholesterol in all groups, suggesting a nephrotic syndrome-like outcome. These results confirmed that kidney tubules are major targets of MeHg nephrotoxicity. Treatment with dietary fats did not prevent, but rather altered the profile of, nephrotoxicity of MeHg in rats.

摘要

将断乳雄性斯普拉格-道利大鼠喂食含大豆油(SO)、海豹油(SE)、二十二碳六烯酸(DHA)、鱼油(FO)或猪油(LA)的半纯化等热量饮食28天,然后每天按0、1或3毫克甲基汞/千克体重灌胃,并喂食相同饮食14天。在尸检当天采集血清和24小时尿液样本,分析肾功能和疾病标志物。分析肾切片的对氨基马尿酸(PAH)和四乙铵(TEA)摄取、总汞和甲基汞含量,并检查病理损伤。所有饮食组的总汞和甲基汞含量均显著且呈剂量依赖性增加。甲基汞显著增加了所有组的相对肾重量,除SO组外所有组的血清肌酐,DHA和LA组的血清尿酸,除LA组外所有组的血清镁,以及SO组的尿蛋白。甲基汞显著降低了SE、FO和LA组的血清尿素氮,DHA组的尿肌酐,除SE组外所有组的PAH摄取,以及所有组的TEA摄取。甲基汞在所有饮食组中均导致肾病。甲基汞还显著增加了除SE组外所有组的中性粒细胞计数,除DHA组外所有组的血清白蛋白和甘油三酯降低,以及所有组的血清总胆固醇增加,提示类似肾病综合征的结果。这些结果证实肾小管是甲基汞肾毒性的主要靶标。饮食脂肪处理并未预防,反而改变了甲基汞对大鼠的肾毒性特征。

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