Aldose reductase inhibition and the phosphorus-31 profile of the intact diabetic rat lens.
Diabetic metabolic change and response to aldose reductase inhibition in the Wistar rat lens were examined with phosphorus-31 (31P) nuclear magnetic resonance (NMR) spectroscopy. To avoid artifacts in sample preparation, we used freshly excised lenses and acquired NMR data for 20 min immediately after lens extraction. The results showed a diabetes-induced time-dependent loss of ATP and phosphorylcholine (PC), an increase in alpha-glycerophosphate (alpha-GP) and inorganic phosphate and the appearance of sorbitol-3-phosphate (S-3-P) and fructose-3-phosphate (F-3-P). Oral but not topical dosing of an aldose reductase inhibitor, 5-(3-ethoxy-4-pentyloxyphenyl)-2,4- thiazolidinedione, resulted in a positive dose-response correlation characterized by a restoration of PC, S-3-P and F-3-P to the prediabetic level; however, alpha-GP and ATP were only partially normalized. The significance of the 31P change was further discussed.
Tsubota
K
K
Department of Ophthalmology, Ichikawa General Hospital, Tokyo Dental College, Chiba, Japan.
Yoshida
M
M
Toda
T
T
Ono
M
M
Kajiwara
K
K
Cheng
H M
HM
D000255:Adenosine Triphosphate / Q000378:metabolism; D000284:Administration, Oral; D000287:Administration, Topical; D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000818:Animals; D050260:Carbohydrate Metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D007908:Lens, Crystalline / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D010710:Phosphates / Q000378:metabolism*; D010759:Phosphorus Isotopes; D051381:Rats; D017208:Rats, Wistar; D013311:Streptozocin; D013844:Thiazoles / Q000494:pharmacology; D045162:Thiazolidinediones
D010710:Phosphates; D010759:Phosphorus Isotopes; D013844:Thiazoles; D045162:Thiazolidinediones; D013311:Streptozocin; C051003:risarestat; D000255:Adenosine Triphosphate; D000449:Aldehyde Reductase