Effect of an aldose reductase inhibitor, SNK-860, on deficits in the electroretinogram of diabetic rats.
To determine the effect of an aldose reductase inhibitor, SNK-860, on the worsening of the electroretinogram (ERG) during a diabetic state, rats with streptozotocin-induced diabetes were administered SNK-860 (1 or 4 mg kg-1 orally) daily for 4 weeks. The effectiveness of SNK-860 in prolonging the peak latencies of oscillatory potentials in the b-wave of the electroretinogram of diabetic rats varied between these different waveform components (designated O1, O2 and O3). SNK-860 (4 mg kg-1 day-1) either completely or partially prevented the prolonged peak latencies at O1 and sigma(O1 + O2 + O3). The drug failed to shorten the latency of the O2 and O3 components, and produced only a modest reduction in retinal levels of sorbitol and fructose, with no increase in myo-inositol. There was a significant correlation between the state of the ERG (components O1 and sigma(O1 + O2 + O3)) and the retinal levels of sorbitol and fructose (P < 0.01), but not of myo-inositol. It is concluded that a better understanding of the mechanism by which SNK-860 acts may provide new insight into the pathogenesis of hyperglycaemic retinal dysfunction and help to establish effective therapy for diabetic retinopathy.
Hotta
N
N
Third Department of Internal Medicine, Nagoya University School of Medicine, Japan.
Koh
N
N
Sakakibara
F
F
Nakamura
J
J
Hamada
Y
Y
Naruse
K
K
Sasaki
H
H
Mizuno
K
K
Matsubara
A
A
Kakuta
H
H
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000818:Animals; D050260:Carbohydrate Metabolism; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D004596:Electroretinography; D007093:Imidazoles / Q000494:pharmacology*; D048289:Imidazolidines; D007294:Inositol / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000187:drug effects* / Q000503:physiopathology*; D013012:Sorbitol / Q000378:metabolism
D007093:Imidazoles; D048289:Imidazolidines; D007294:Inositol; D013012:Sorbitol; C077139:fidarestat; D000449:Aldehyde Reductase