MODIFICATION OF THE GLYOXALASE SYSTEM IN STREPTOZOTOCIN-INDUCED DIABETIC RATS - EFFECT OF THE ALDOSE REDUCTASE INHIBITOR STATIL
MODIFICATION OF THE GLYOXALASE SYSTEM IN STREPTOZOTOCIN-INDUCED DIABETIC RATS - EFFECT OF THE ALDOSE REDUCTASE INHIBITOR STATIL
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DOI：
10.1016/0006-2952(93)90488-i
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发表时间：
1993-09-01
影响因子：
5.8
通讯作者：
THORNALLEY, PJ
中科院分区：
文献类型：
--
作者：
PHILLIPS, SA;MIRRLEES, D;THORNALLEY, PJ
在链脲佐菌素诱导的糖尿病大鼠和正常对照的组织（肝脏、骨骼肌、肾皮质和髓质、透镜和坐骨神经）和血液中表征了谷胱甘肽酶系统。还研究了醛糖还原酶抑制剂Statil [3-（4-溴-2-氟苄基）-4-氧代-3H-酞嗪-1-基-乙酸; ICI 128 436]的作用。相对于正常对照组，糖尿病大鼠和他汀治疗的糖尿病大鼠的肝脏中的谷胱甘肽酶I和谷胱甘肽酶II活性降低，骨骼肌中的谷胱甘肽酶II活性升高。与正常对照组相比，糖尿病大鼠肝脏和透镜中非蛋白巯基（NPSH）的浓度降低; Statil可防止这些影响。糖尿病大鼠肾皮质、髓质、透镜和血液中丙酮醛浓度均高于正常对照组。除肾皮质外，Statil阻止了这些增加。与正常对照组相比，糖尿病大鼠的透镜和血液中D-乳酸盐浓度升高，Statil可部分阻止血液中D-乳酸盐浓度升高，但不能阻止透镜中D-乳酸盐浓度升高。这些数据表明，在链脲佐菌素诱导的糖尿病大鼠的组织和血液中，谷胱甘肽酶系统被修改，并且其中一些修改可以被Statil阻止。肾脏、透镜和血液中丙酮醛浓度升高，以及透镜中NPSH浓度降低可能与糖尿病并发症的发生有关。
The glyoxalase system was characterized in tissue (liver, skeletal muscle, kidney cortex and medulla, lens and sciatic nerve) and blood from streptozotocin-induced diabetic rats and normal controls. The effect of the aldose reductase inhibitor, Statil [3-(4-bromo-2-fluorobenzyl)-4-oxo-3H-phthalazine-1-yl-acetic acid; ICI 128 436], was also investigated. Glyoxalase I and glyoxalase II activities were decreased in the liver and increased in skeletal muscle of diabetic rats and of Statil-treated diabetic rats, relative to normal controls. The concentration of non-protein sulphydryl (NPSH) was decreased in the liver and lens of diabetic rats, relative to normal controls; Statil prevented these effects. The concentrations of methylglyoxal in the kidney cortex and medulla, lens and blood were increased in diabetic rats, relative to normal controls. Statil prevented these increases except in the kidney cortex. The concentration of D-lactate was increased in the lens and blood of diabetic rats, relative to normal controls, which was partially prevented in blood but not in the lens by Statil. These data suggest that the glyoxalase system is modified in tissues and blood of streptozotocin-induced diabetic rats and some of the modifications may be prevented by Statil. The increased concentrations of methylglyoxal in the kidney, lens and blood, and the decreased concentration of NPSH in the lens may be related to the development of diabetic complications.