Antidiabetic Activity and Inhibitory Effects of Derivatives of Advanced Aminoguanidine Glycation

Abstract

Aminoguanidine is a drug that prevents the formation of AGEs by reacting with initial glycation products and is effective in improving proteinuria and vessel elasticity, preventing diabetic retinopathy, and treating patients with diabetic nephropathy. Structural modifications of this molecule were carried out, and 19 derivatives were studied to present a potential hypoglycemic and antiglicante effect, preventing such complications for diabetics. For this purpose, an in vitro cytotoxicity test was initially carried out by colorimetric assay with MTT [3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium], in macrophages of the J774 lineage. The AGEs were produced in vitro from the junction of glucose with bovine serum albumin and tested for evaluation of the antiglicante activity with reading in a fluorescence spectrophotometer. Derivatives with the best in vitro response were submitted to in vivo acute toxicity tests with Wistar rats and later evaluation of their antidiabetic and antiglycant potential in rats with streptozotocin-induced diabetes. After euthanasia, the heart, kidney, liver, and pancreas were removed for histopathological examination, and the blood for blood count and glycated hemoglobin, glucose, insulin, triglycerides, total cholesterol, HDL cholesterol, serum albumin, fructosamine, TGO, TGP, and GGT were collected. It is possible to conclude that the studied derivatives have the potential for the production of a drug that can be produced with them or associated with them and that is capable of reducing the glycemic indices and, at the same time, having an antiglicant action protecting individuals from macro- and microvascular complications.