scholarly journals Comparison of the effects of inhibitors of aldose reductase and sorbitol dehydrogenase on neurovascular function, nerve conduction and tissue polyol pathway metabolites in streptozotocin-diabetic rats

Diabetologia ◽  
1997 ◽  
Vol 40 (3) ◽  
pp. 271-281 ◽  
Author(s):  
N. E. Cameron ◽  
M. A. Cotter ◽  
M. Basso ◽  
T. C. Hohman
Keyword(s):  
Aldose Reductase ◽  
Nerve Conduction ◽  
Polyol Pathway ◽  
Diabetic Rats ◽  
Sorbitol Dehydrogenase ◽  
Streptozotocin Diabetic Rats

scholarly journals A Novel Carboxymethylated Mercaptotriazinoindole Inhibitor of Aldose Reductase Interferes With the Polyol Pathway in Streptozotocin-Induced Diabetic Rats

2015 ◽  
pp. 587-591 ◽  
Author(s):  
M. SOLTESOVA PRNOVA ◽  
J. BALLEKOVA ◽  
A. GAJDOSIKOVA ◽  
A. GAJDOSIK ◽  
M. STEFEK
Keyword(s):  
Sciatic Nerve ◽  
Aldose Reductase ◽  
Experimental Diabetes ◽  
Polyol Pathway ◽  
Diabetic Rats ◽  
Sorbitol Dehydrogenase ◽  
Substrate Affinity ◽  
Back Reaction ◽  
Forward Reaction

The aim of the present work was to study the effect of 3-mercapto-5H-1,2,4-triazino[5,6-b]indole-5-acetic acid (CMTI), an efficient aldose reductase inhibitor, on sorbitol accumulation in selected organs of streptozotocin-induced diabetic rats in vivo. In addition, the effect of CMTI on aldose reductase back reaction and on sorbitol dehydrogenase was determined. The model of experimental diabetes in male Wistar rats induced by streptozotocin was used. Experimental diabetes was induced by triple intraperitoneal doses of streptozotocin on three consecutive days. In diabetic rats, significant elevation of sorbitol concentration in the sciatic nerve and eye lenses was recorded. CMTI administered intragastrically (50 mg/kg/day) for five consecutive days significantly inhibited sorbitol accumulation in the sciatic nerve, yet it was without effect in eye lenses of diabetic animals. For aldose reductase back reaction, the substrate affinity of glycerol to aldose reductase was one order lower than that of glyceraldehyde in forward reaction. In addition, the back reaction was much slower, characterized by Vmax value of about 30 times lower than that of the forward reaction. Inhibition of aldose reductase by CMTI was characterized by closely related IC50 values in submicromolar range for both forward and back reactions. No significant inhibition of the second enzyme of the polyol pathway, sorbitol dehydrogenase, by 100 μM CMTI was recorded (I=0.9±2.7 %, n=3). To conclude, the presented results showed the ability of CMTI to affect the polyol pathway in diabetic rats in vivo and represent thus a further step in a complex preclinical evaluation of CMTI as a potential agent for treatment of chronic diabetic complications.

Beneficial influence of fungal metabolite nigerloxin on eye lens abnormalities in experimental diabetes

2012 ◽  
Vol 90 (4) ◽  
pp. 387-394 ◽  
Author(s):  
Bharathinagar S. Suresha ◽  
Avinash P. Sattur ◽  
Krishnapura Srinivasan
Keyword(s):  
Aldose Reductase ◽  
Radical Scavenging ◽  
Lipid Peroxides ◽  
Antioxidant Defense System ◽  
Polyol Pathway ◽  
Diabetic Rats ◽  
Sorbitol Dehydrogenase ◽  
Eye Lens ◽  
Fungal Metabolite

Osmotic and oxidative stress have been implicated in the pathogenesis of diabetic cataract. Nigerloxin, a fungal metabolite, has been shown to possess aldose reductase inhibitory and free radical scavenging potential, in vitro. In the present study, the beneficial influence of nigerloxin was investigated on diabetes-induced alteration in the eye lens of rats treated with streptozotocin. Groups of diabetic rats were administered nigerloxin orally (100 mg·(kg body mass)–1·day–1) for 30 days. The activity of lens polyol pathway enzymes (aldose reductase and sorbitol dehydrogenase), lipid peroxides, and advanced glycation end products (AGEs) were increased in the diabetic animals. Levels of glutathione as well as the activity of antioxidant enzymes (superoxide dismutase, glutathione-S-transferase, and glutathione peroxidase) were decreased in the eye lens of the diabetic animals. The administration of nigerloxin significantly decreased levels of lipid peroxides and AGEs in the lens of the diabetic rats. Increase in the activity of aldose reductase and sorbitol dehydrogenase in the lens was countered by nigerloxin treatment. The activity of glutathione and antioxidant enzyme in the lens was significantly elevated in nigerloxin-treated diabetic rats. Examination of the treated rats’ eyes indicated that nigerloxin delayed cataractogenesis in the diabetic rats. The results suggest the beneficial countering of polyol pathway enzymes and potentiation of the antioxidant defense system by nigerloxin in diabetic animals, implicating its potential in ameliorating cataracts in diabetics.

scholarly journals Glycation and inactivation of sorbitol dehydrogenase in normal and diabetic rats

1996 ◽  
Vol 318 (1) ◽  
pp. 119-123 ◽  
Author(s):  
Ayumu HOSHI ◽  
Motoko TAKAHASHI ◽  
Junichi FUJII ◽  
Theingi MYINT ◽  
Hideaki KANETO ◽  
...  
Keyword(s):  
Enzyme Activity ◽  
Diabetic Complications ◽  
Polyol Pathway ◽  
Diabetic Rats ◽  
Sorbitol Dehydrogenase ◽  
Enzyme Content ◽  
Glycated Protein ◽  
Liver And Kidney

Sorbitol dehydrogenase (SDH) is involved in the polyol pathway, which plays an important role in the pathogenesis of diabetic complications. We have measured the tissue distributions of SDH mRNA, both the immunoreactive enzyme levels and the enzyme activity. SDH mRNA was especially abundant in liver, kidney and testis. Both the activity and enzyme content are high in liver and kidney but not in testis. The discrepancy between mRNA and immunoreactive enzyme levels and the activity of SDH observed in testis was also seen in livers of streptozotocin-induced diabetic rats. SDH was found to exist in both glycated and non-glycated forms, with larger amounts of the glycated protein in the diabetic liver. Moreover, after incubation of purified enzyme with glucose or fructose, its activity was markedly decreased. These results indicate that glycation causes a decrease in SDH activity in liver under diabetic conditions. The same post-transcriptional event might occur to decrease the activity of SDH in testis in normal animals.

Sorbinil prevents glomerular hyperperfusion in diabetic rats

1989 ◽  
Vol 256 (6) ◽  
pp. F1000-F1006 ◽  
Author(s):  
N. Bank ◽  
P. Mower ◽  
H. S. Aynedjian ◽  
B. M. Wilkes ◽  
S. Silverman
Keyword(s):  
Aldose Reductase ◽  
Muscle Tone ◽  
Plasma Renin ◽  
Insulin Dependent Diabetes Mellitus ◽  
Polyol Pathway ◽  
Diabetic Rats ◽  
Dependent Diabetes Mellitus ◽  
Ang Ii ◽  
Receptor Sites ◽  
Single Nephron

The role of polyol pathway metabolism in glomerular hyperperfusion of insulin-dependent diabetes mellitus (IDDM) was studied in rats. Streptozotocin-induced diabetic rats were fed the aldose reductase inhibitor, sorbinil (8 mg/day). Untreated diabetic rats and normal rats served as controls. All groups were fed the same diet, rationed to 20 g/day. Micropuncture, plasma renin activity (PRA), and glomerular angiotensin II (ANG II)-receptor measurements were made 7-15 days after streptozotocin injection. Untreated diabetic rats had higher than normal single-nephron filtration rate (SNGFR), plasma flow (QA), and blood flow (SNBF), and reduced afferent resistance. Glomerular ANG II-receptor sites were markedly decreased. In diabetic rats fed sorbinil SNGFR, QA, and SNBF were all lower than in untreated diabetic rats, and indistinguishable from values in normal rats. However, single-nephron filtration fraction (SNFF) rose above normal. PRA, glomerular ANG II receptors, and blood glucose were not affected by sorbinil. In normal rats fed sorbinil, SNGFR, QA, and SNBF were not significantly different than in normal rats. Our observations are consistent with the view that polyol pathway metabolism plays a role in glomerular hyperperfusion in IDDM. Inhibition of aldose reductase increased vascular smooth muscle tone at pre- and probably postglomerular sites.

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