Amelioration of diabetes and cataract by Na3VO4 plus U-83836E in streptozotocin treated rats.
Experimental work in our laboratory has confirmed the protective activity of vanadium compounds on hyperglycemia and glycosuria in streptozotocin (STZ) diabetes. Furthermore, diabetic cataract has also been partially prevented. Nevertheless, the combination of a natural antioxidant, vitamin E, with Na3 VO4 has not further enhanced this ameliorating effect. Our experimental approach has been an attempt to block the prooxidant activity of both STZ and vanadate, with the purpose of eliciting the best possible antidiabetic protection. More recently, a lipid soluble synthetic antioxidant U-78517F, a 2-methylaminochroman, has been reported to have a significant protective effect against brain injury and ischemia. This compound inhibits the iron-dependent lipid peroxidation 100 times more effectively than vitamin E. This investigation has introduced a combination of the vanadium compound plus the aforesaid lazaroid, as its (-) enantiomer, U-83836E, in order to improve the insufficient protection when vitamin E was used. For twelve weeks, male Wistar rats, rendered diabetic with STZ, were administered Na3VO4 in drinking water along with the lazaroid carried by the food. Four, eight and twelve weeks after the beginning of the protective treatment, fluid and food intake, diuresis and excreted feces, glycosuria and proteinuria were determined on biological samples obtained in metabolic cages; body weight and glycemia were also recorded. At weeks 6 and 12 of the treatment, the opaqueness of the eye lenses was controlled and registered. At the end of the experiment, circulating glycosylated hemoglobin (HbA1c), fructosamine, N-acetyl-beta-D-glucosaminidase (NAG), and fluorescent peroxides were evaluated. Within the first month of treatment, protection by the combination paralleled that elicited by vanadate alone. At subsequent steps, U-83836E significantly improved the protective effect of vanadate alone on polydipsia and polyuria, but especially on hyperglycemia and glycosuria. The further ameliorating effect of the lazaroid was also observed on HbA1c and NAG, and, most important, on the cataract. In conclusion, these findings demonstrate that the lazaroid U-83836E succeeds in further protecting the most important symptoms of diabetes treated with vanadate, and that this antioxidant acts effectively even when it is administered orally in food, in a non invasive manner.
Ugazio
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Dipartimento di Medicina e Oncologia Sperimentale, Sezione di Patologia Ambientale, Torino, Italia.
Bosia
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Burdino
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Grignolo
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D000118:Acetylglucosaminidase / Q000097:blood; D000818:Animals; D002386:Cataract / Q000097:blood / Q000139:chemically induced / Q000517:prevention & control*; D002839:Chromans / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000517:prevention & control*; D004359:Drug Therapy, Combination; D016166:Free Radical Scavengers; D019270:Fructosamine; D006442:Glycated Hemoglobin / Q000032:analysis; D006595:Hexosamines / Q000097:blood; D007908:Lens, Crystalline / Q000187:drug effects; D008297:Male; D010545:Peroxides / Q000097:blood; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D013311:Streptozocin; D014638:Vanadates / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use
D000118:Acetylglucosaminidase; D002839:Chromans; D016166:Free Radical Scavengers; D019270:Fructosamine; D006442:Glycated Hemoglobin; D006595:Hexosamines; D010545:Peroxides; D010879:Piperazines; D013311:Streptozocin; D014638:Vanadates; C066382:U 78517F