Attenuation of hyperglycemia and amadori products by aminoguanidine in alloxan-diabetic rabbits occurs via enhancement in antioxidant defenses and control of stress

• Published in: PloS one 2022-01, Vol.17 (1), p.e0262233
• Main Authors: Arif, Binish, Arif, Zarina, Ahmad, Jamal, Perveen, Kahkashan, Bukhari, Najat A, Ashraf, Jalaluddin M, Moinuddin, Alam, Khursheed
• Format: Article
• Language: English
• Subjects: Adducts; Advanced glycation end products; Advanced glycosylation end products; Age; Alloxan; Amadori compounds; Aminoguanidine; Animals; Antioxidants; Antioxidants - administration & dosage; Antioxidants - pharmacology; Attenuation; Biochemistry; Biology and Life Sciences; Body weight; Carbonyl compounds; Carbonyls; Care and treatment; Case-Control Studies; Catalase; Catalase - metabolism; Chemicals; Complications; Complications and side effects; Diabetes; Diabetes mellitus; Diabetes Mellitus, Experimental - chemically induced; Diabetes Mellitus, Experimental - drug therapy; Diabetes Mellitus, Experimental - metabolism; Diabetes Mellitus, Type 1 - chemically induced; Diabetes Mellitus, Type 1 - drug therapy; Diabetes Mellitus, Type 1 - metabolism; Drug Administration Schedule; Drug dosages; Free radicals; Gene Expression Regulation - drug effects; Glucose; Glutathione; Glutathione - metabolism; Glutathione peroxidase; Glutathione Peroxidase - metabolism; Glycosylation; Guanidines - administration & dosage; Guanidines - pharmacology; Health aspects; Hemoglobin; Hyperglycemia; Hyperglycemia - chemically induced; Hyperglycemia - drug therapy; Hyperglycemia - metabolism; Injection; Insulin; Intravenous administration; Lipid Peroxidation - drug effects; Lipids; Medical schools; Medicine; Medicine and Health Sciences; Nitric oxide; Nitric Oxide - metabolism; Oxidative Stress - drug effects; Peroxidase; Peroxides; Proteins; Rabbits; Research and Analysis Methods; Risk reduction; Superoxide dismutase; Superoxide Dismutase - metabolism; Testing
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0262233

The micro- and macro-complications in diabetes mellitus (DM) mainly arise from the damage induced by Amadori and advanced glycation end products, as well as the released free radicals. The primary goal of DM treatment is to reduce the risk of micro- and macro-complications. In this study, we looked at the efficacy of aminoguanidine (AG) to prevent the production of early glycation products in alloxan-diabetic rabbits. Type1 DM was induced in rabbits by a single intravenous injection of alloxan (90 mg/kg body weight). Another group of rabbits was pre-treated with AG (100 mg/kg body weight) prior to alloxan injection; this was followed by weekly treatment with 100 mg/kg of AG for eight weeks. Glucose, insulin, and early glycation products (HbA1C and fructosamine) were measured in control, diabetic and AG treated diabetic rabbits. The effects of hyperglycemia on superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (Gpx), reduced glutathione (rGSH), nitric oxide, lipid peroxides, and protein carbonyl were investigated. Alloxan-diabetic rabbits had lower levels of SOD, CAT, Gpx, and rGSH than control rabbits. Nitric oxide levels were considerably greater. AG administration restored the activities of SOD, CAT, Gpx enzymes up to 70-80% and ameliorated the nitric oxide production. HbA1c and fructosamine levels were considerably lower in AG-treated diabetic rabbits. The observed control of hyperglycemia and amadori adducts in alloxan-diabetic rabbits by AG may be attributed to decrease of stress and restoration of antioxidant defenses.