Modification of the glyoxalase system in streptozotocin-induced diabetic rats. Effect of the aldose reductase inhibitor Statil.
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.
Phillips
S A
SA
Department of Chemistry and Biological Chemistry, University of Essex, Colchester, U.K.
Mirrlees
D
D
Thornalley
P J
PJ
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000818:Animals; D001786:Blood Glucose; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology*; D007668:Kidney / Q000201:enzymology; D007773:Lactates / Q000097:blood; D007791:Lactoylglutathione Lyase / Q000378:metabolism*; D008099:Liver / Q000201:enzymology; D008297:Male; D009132:Muscles / Q000201:enzymology; D010793:Phthalazines / Q000494:pharmacology*; D011765:Pyruvaldehyde / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D013438:Sulfhydryl Compounds / Q000032:analysis; D013869:Thiolester Hydrolases / Q000378:metabolism*; D000099301:Hydroxyacylglutathione Hydrolase
D000449:Aldehyde Reductase; D001786:Blood Glucose; D007773:Lactates; D007791:Lactoylglutathione Lyase; D010793:Phthalazines; D011765:Pyruvaldehyde; D013438:Sulfhydryl Compounds; D013869:Thiolester Hydrolases; D000099301:Hydroxyacylglutathione Hydrolase; C042829:ponalrestat