Dietary glycotoxins - Inhibition of reactive products by aminoguanidine facilitates renal clearance and reduces tissue sequestration
Dietary glycotoxins - Inhibition of reactive products by aminoguanidine facilitates renal clearance and reduces tissue sequestration
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DOI：
10.2337/diabetes.48.6.1308
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发表时间：
1999-06-01
期刊：
影响因子：
7.7
通讯作者：
Vlassara, H
中科院分区：
文献类型：
--
作者：
He, CJ;Sabol, J;Vlassara, H
有证据表明，口服吸收的食物源反应性晚期糖基化终末产物 (AGE) 或糖毒素 (GT) 的代谢周转被延迟，可能导致内源性 AGE 引起的组织损伤，尤其是在糖尿病和肾病患者中。本研究的目的是探讨氨基胍 (AG) 对膳食 AGE 生物反应性的药理学抑制是否可以改善这些物质的周转和肾脏排泄。正常 Sprague-Dawley 大鼠喂食单标记 [C-14]AGE-卵清蛋白、双标记 [C-14-I-125]AGE-卵清蛋白或对照 I-125 标记卵清蛋白饮食加游离 [C-14] 葡萄糖，有或没有 AG（0.2% 水溶液）。将 [C-14]AGE 和 I-125 标记的肽相关放射性 (RA) 与组织、血清和 72 小时尿液样本中的 AGE 免疫反应性（通过酶联免疫吸附测定法）进行比较。在含有或不含 AG 的标记膳食 AGE 进餐后，通过监测纤连蛋白 (FN) 肽片段和血清成分之间共价复合物形成的抑制来评估 AG 对膳食 AGE 生物反应性的影响。放射性标记的 AGE 饮食产生的血清吸收和尿液排泄峰值在动力学上与游离 [C-14] 葡萄糖或 [I-125] 卵清蛋白的峰值不同。约 26% 口服吸收的 AGE-卵清蛋白通过尿液排出，而 AG 治疗后，饮食中 AGE 的尿液排泄显着增加（> 吸收的 50%）。超过 60% 的组织结合 RA 共价沉积在肾脏和肝脏中，而使用 AG 治疗后，组织 AGE 沉积减少至
Evidence indicates that the metabolic turnover of food-derived reactive orally absorbed advanced glycation end products (AGEs) or glycotoxins (GTs) is delayed, possibly contributing to the tissue damage induced by endogenous AGEs, especially in patients with diabetes and kidney disease. The aim of this study was to explore whether pharmacologic inhibition of dietary AGE bioreactivity by aminoguanidine (AG) can improve turnover and renal excretion of these substances. Normal Sprague-Dawley rats were fed single-labeled [C-14]AGE-ovalbumin, double-labeled [C-14-I-125]AGE-ovalbumin, or control I-125-labeled ovalbumin diet plus free [C-14]glucose, with or without AG (0.2% in water). [C-14]AGE- and I-125-labeled peptide-associated radioactivity (RA) were compared with AGE immunoreactivity (by enzyme-linked immunosorbent assay) in tissues, serum, and 72-h urine samples. The effect of AG on dietary AGE bioreactivity was assessed by monitoring the inhibition of covalent complex formation between fibronectin (FN) peptide fragments and serum components, after a meal of labeled dietary AGE with or without AG. The radiolabeled AGE diet produced serum absorption and urinary excretion peaks kinetically distinct from those of free [C-14]glucose or [I-125]ovalbumin. Some 26% of the orally absorbed AGE-ovalbumin was excreted in the urine, whereas after AG treatment, urinary excre-tion of dietary AGEs increased markedly (to >50% of absorbed). More than 60% of tissue-bound RA was found covalently deposited in kidneys and liver, whereas after treatment with AG, tissue AGE deposits were reduced to