title: Preventive Effect of Salicylate and Pyridoxamine on Diabetic Nephropathy.
abstract: Objective. Diabetic nephropathy is a life-threatening complication in patients with long-standing diabetes. Hemodynamic, inflammatory, and metabolic factors are considered as developmental factors for diabetic nephropathy. In this study, we evaluated whether pharmacological interventions with salicylate, compared to pyridoxamine, could prevent diabetic nephropathy in mice.Methods. Male mice overexpressing inducible nitric oxide synthase in pancreaticβ-cells were employed as a diabetic model. Salicylate (3 g/kg diet) or pyridoxamine (1 g/L drinking water; ~200 mg/kg/day) was given for 16 weeks to assess the development of diabetic nephropathy. Treatment with long-acting insulin (Levemir 2 units/kg twice a day) was used as a control.Results. Although higher blood glucose levels were not significantly affected by pyridoxamine, early to late stage indices of nephropathy were attenuated, including kidney enlargement, albuminuria, and increased serum creatinine, glomerulosclerosis, and inflammatory and profibrotic gene expressions. Salicylate showed beneficial effects on diabetic nephropathy similar to those of pyridoxamine, which include lowering blood glucose levels and inhibiting macrophage infiltration into the kidneys. Attenuation of macrophage infiltration into the kidneys and upregulation of antiglycating enzymeglyoxalase 1gene expression were found only in the salicylate treatment group.Conclusions. Treatment with salicylate and pyridoxamine could prevent the development of diabetic nephropathy in mice and, therefore, would be a potentially useful therapeutic strategy against kidney problems in patients with diabetes.
authors.affiliation: Department of Biochemistry and Molecular Vascular Biology, Kanazawa University Graduate School of Medical Sciences, 13-1 Takara-machi, Kanazawa 920-8640, Japan; Department of Biochemistry, Faculty of Veterinary Medicine, Kafrelsheikh University, Kafr El Sheikh 33516, Egypt.
authors.forename: Tarek Kamal
authors.initials: TK
authors.lastname: Abouzed
authors.affiliation: Department of Biochemistry and Molecular Vascular Biology, Kanazawa University Graduate School of Medical Sciences, 13-1 Takara-machi, Kanazawa 920-8640, Japan.
authors.forename: Seiichi
authors.initials: S
authors.lastname: Munesue
authors.affiliation: Department of Biochemistry and Molecular Vascular Biology, Kanazawa University Graduate School of Medical Sciences, 13-1 Takara-machi, Kanazawa 920-8640, Japan.
authors.forename: Ai
authors.initials: A
authors.lastname: Harashima
authors.affiliation: Molecular Pharmacotherapeutics, Faculty of Pharmacy, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Masuo
authors.affiliation: Molecular Pharmacotherapeutics, Faculty of Pharmacy, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Japan.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Kato
authors.affiliation: Department of Biochemistry, Faculty of Veterinary Medicine, Kafrelsheikh University, Kafr El Sheikh 33516, Egypt.
authors.forename: Khaled
authors.initials: K
authors.lastname: Khailo
authors.affiliation: Department of Biochemistry and Molecular Vascular Biology, Kanazawa University Graduate School of Medical Sciences, 13-1 Takara-machi, Kanazawa 920-8640, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yamamoto
authors.affiliation: Department of Biochemistry and Molecular Vascular Biology, Kanazawa University Graduate School of Medical Sciences, 13-1 Takara-machi, Kanazawa 920-8640, Japan.
authors.forename: Yasuhiko
authors.identifier: 0000-0003-1326-4649
authors.initials: Y
authors.lastname: Yamamoto
mesh_terms: D000419:Albuminuria / Q000209:etiology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D001786:Blood Glucose / Q000032:analysis / Q000378:metabolism; D003404:Creatinine / Q000097:blood; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000378:metabolism; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000517:prevention & control*; D005434:Flow Cytometry; D006439:Hemodynamics; D007249:Inflammation; D049528:Insulin, Long-Acting / Q000494:pharmacology; D050417:Insulin-Secreting Cells / Q000187:drug effects; D007668:Kidney / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D011733:Pyridoxamine / Q000627:therapeutic use*; D012459:Salicylates / Q000627:therapeutic use*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D001786:Blood Glucose; D049528:Insulin, Long-Acting; D012459:Salicylates; D011733:Pyridoxamine; D003404:Creatinine; D052247:Nitric Oxide Synthase Type II