An aldose reductase inhibitor, TAT, prevents electroretinographic abnormalities and ADP-induced hyperaggregability in streptozotocin-induced diabetic rats.
Rats with streptozotocin-induced diabetes were oral given TAT, a potent aldose reductase inhibitor, at a dose of 10 mg kg-1 day-1 or 40 mg kg-1 day-1 for 30 days. Prolongation of the peak latency of oscillatory potentials in the b-wave of the electroretinogram (ERG), which is associated with retinal Müller cell dysfunction, was significantly improved by treatment with TAT as compared with untreated diabetic rats [sigma(O1 + O2 + O3) was 106.8 +/- 1.8 ms in normal controls (NC), 118.2 +/- 1.1 ms in diabetic controls (DC) (P < 0.001 vs. NC), 110.8 +/- 1.5 ms with 10 mg kg-1 TAT (P < 0.001 vs. DC) and 111.4 +/- 1.6 ms with 40 mg kg-1 TAT (P < 0.01 vs. DC)]. The improvement in ERG abnormalities in diabetic rats was accompanied by partial reduction of elevated sorbitol levels in the retina and erythrocytes, and by correction of platelet hyperaggregability. The authors' findings suggest that a better understanding of the mechanism by which TAT acts may provide new insights into the pathogenesis of hyperglycaemic retinal dysfunction and contribute to establishing effective therapy for diabetic retinopathy.
Hotta
N
N
The Third Department of Internal Medicine, Nagoya University School of Medicine, Japan.
Koh
N
N
Sakakibara
F
F
Nakamura
J
J
Hamada
Y
Y
Hara
T
T
Takeuchi
N
N
Inukai
S
S
Kasama
N
N
Fukasawa
H
H
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000503:physiopathology*; D003930:Diabetic Retinopathy / Q000517:prevention & control*; D004596:Electroretinography / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D005632:Fructose / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000503:physiopathology*; D013012:Sorbitol / Q000378:metabolism; D013777:Tetrazoles / Q000494:pharmacology* / Q000627:therapeutic use; D013876:Thiophenes / Q000494:pharmacology* / Q000627:therapeutic use
D004791:Enzyme Inhibitors; D013777:Tetrazoles; D013876:Thiophenes; C080974:(5-(3-thienyl)tetrazol-1-yl)acetic acid; D005632:Fructose; D013012:Sorbitol; D000244:Adenosine Diphosphate; D000449:Aldehyde Reductase; D005947:Glucose