In vivo formation of a Schiff base of aminoguanidine with pyridoxal phosphate.

In vivo formation of a Schiff base of aminoguanidine with pyridoxal phosphate.
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氨基胍与磷酸吡哆醛在体内形成希夫碱。

DOI:
10.1016/s0006-2952(98)00010-0
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发表时间:
1998
影响因子:
5.8
通讯作者:
I. Miwa
I. Miwa
中科院分区:
医学2区
文献类型:
--
作者:
T. Taguchi;M. Sugiura;Y. Hamada;I. Miwa

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氨基胍(AG)被认为是治疗糖尿病并发症的一种很有前途的化合物。我们研究了AG与5′-磷酸吡哆醛(PLP)和吡哆醛(PL)的希夫碱在体外和体内的形成。AG在体外与PLP反应生成Schiff碱(PLP-AG)的速度远快于与PL反应生成Schiff碱(PL-AG)的速度。在饮用水中以7 mM施用AG 18周引起小鼠肝脏和肾脏中PLP-AG的形成(分别为12.1 ± 1.6和3.8 ± 0.64nmol/g组织,平均值± SD,N = 6)。施用AG的小鼠肝脏中PLP的量显著低于对照小鼠(4.0 ± 1.4 vs 17.4 ± 1.3 nmol/g湿组织,平均值± SD,N = 6)。吡哆醇(饮用水中1 mM)与AG(饮用水中7 mM)同时给药并不能改善组织PLP的降低,并导致PLP-AG的过量形成。提示临床应用AG时应注意组织PLP的不足。
Aminoguanidine (AG) is considered to be a promising compound for the treatment of diabetic complications. We examined the in vitro and in vivo formation of Schiff bases of AG with pyridoxal 5′-phosphate (PLP) and pyridoxal (PL). AG reacted in vitro far more rapidly with PLP to form a Schiff base (PLP–AG) than with PL to form another Schiff base (PL–AG). Administration of AG at 7 mM in drinking water for 18 weeks caused the formation of PLP–AG in the liver and kidney of mice (12.1 ± 1.6 and 3.8 ± 0.64 nmol/g of tissue, respectively, mean ± SD, N = 6). The amount of PLP in the liver of mice AG administered was significantly lower than that of control mice (4.0 ± 1.4 vs 17.4 ± 1.3 nmol/g of wet tissue, mean ± SD, N = 6). Simultaneous administration of pyridoxine (1 mM in drinking water) with AG (7 mM in drinking water) did not ameliorate the decrease in tissue PLP and caused the excess formation of PLP–AG. The results suggest that attention should be paid to the deficiency of tissue PLP in the clinical use of AG.
DOI: 10.1006/bbrc.1996.0366
发表时间: 1996-03-07
影响因子: 3.1
作者:
Booth, AA;Khalifah, RG;Hudson, BG
通讯作者: Hudson, BG