Phillips S A, Mirrlees D, Thornalley P J
Department of Chemistry and Biological Chemistry, University of Essex, Colchester, U.K.
Biochem Pharmacol. 1993 Sep 1;46(5):805-11. doi: 10.1016/0006-2952(93)90488-i.
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.
对链脲佐菌素诱导的糖尿病大鼠和正常对照大鼠的组织(肝脏、骨骼肌、肾皮质和髓质、晶状体和坐骨神经)及血液中的乙二醛酶系统进行了表征。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。与正常对照相比,糖尿病大鼠和接受Statil治疗的糖尿病大鼠肝脏中的乙二醛酶I和乙二醛酶II活性降低,骨骼肌中的活性升高。与正常对照相比,糖尿病大鼠肝脏和晶状体中的非蛋白巯基(NPSH)浓度降低;Statil可防止这些影响。与正常对照相比,糖尿病大鼠肾皮质和髓质、晶状体和血液中的甲基乙二醛浓度升高。除肾皮质外Statil可防止这些升高。与正常对照相比,糖尿病大鼠晶状体和血液中的D-乳酸浓度升高,Statil可部分防止血液中的升高,但不能防止晶状体中的升高。这些数据表明,链脲佐菌素诱导的糖尿病大鼠的组织和血液中的乙二醛酶系统发生改变部分改变可能可被Statil防止。肾脏、晶状体和血液中甲基乙二醛浓度升高以及晶状体中NPSH浓度降低可能与糖尿病并发症的发生有关。