Aminoguanidine pyridoxal adduct is superior to aminoguanidine for preventing diabetic nephropathy in mice
Aminoguanidine pyridoxal adduct is superior to aminoguanidine for preventing diabetic nephropathy in mice
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DOI：
10.1055/s-2002-33478
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发表时间：
2002-07-01
影响因子：
2.2
通讯作者：
Koike, T
中科院分区：
文献类型：
--
作者：
Miyoshi, H;Taguchi, T;Koike, T
氨基胍抑制晚期糖基化终产物的形成，并已在动物中进行了广泛的研究。然而，氨基胍的给药降低了磷酸吡哆醛的肝脏含量。为了避免这个问题，我们开发了一种氨基胍吡哆醛席夫碱加合物，并在体外以及糖尿病肾病模型中检测其疗效。用氨基胍或氨基胍吡哆醛加合物治疗链脲佐菌素诱导的糖尿病小鼠9周。还进行了体外研究以评估氨基胍及其吡哆醛加合物的抗氧化活性。两种药物均未改变血糖控制。氨基胍吡哆醛加合物能显著改善糖尿病大鼠尿白蛋白排泄，与糖尿病对照组相比，尿白蛋白排泄量增加78.1%，对肾脏病理的进展也有更好的预防作用。两种药物对糖基化的抑制作用相似，但吡哆醛加合物的抗氧化活性要上级得多。这些发现表明，氨基胍吡哆醛加合物可能上级于氨基胍，因为它不仅可以预防维生素B-6缺乏症，而且还可以更好地控制糖尿病肾病，因为这种加合物可以抑制氧化和糖化。
Aminoguanidine inhibits the formation of advanced glycation end-products, and has been extensively examined in animals. However, administration of aminoguanidine decreases the hepatic content of pyridoxal phosphate. In order to avoid this problem, we developed an aminoguanidine pyridoxal Schiff base adduct and examined its efficacy in vitro as well as in a model of diabetic nephropathy. Mice with streptozotocin-induced diabetes were treated with aminoguanidine or aminoguanidine pyridoxal adduct for 9 weeks. An in vitro study was also performed to assess the antioxidant activity of aminoguanidine and its pyridoxal adduct. Neither drug altered glycemic control. Aminoguanidine pyridoxal adduct significantly improved urinary albumin excretion by 78.1% compared with the diabetic control, and also had a better preventive effect on the progression of renal pathology than aminoguanidine did. Inhibition of glycation by both drugs was similar, but the antioxidant activity of the pyridoxal adduct was far superior. These findings suggest that aminoguanidine pyridoxal adduct may be superior to aminoguanidine, as it not only prevents vitamin B-6 deficiency but is also better at controlling diabetic nephropathy, as this adduct inhibits oxidation as well as glycation.