OBJECTIVES: The thickening of the glomerular basement membrane in rats after Vacor ingestion was examined by electron microscopy. This study was performed to elucidate which biochemical components changed in the glomerular basement membrane after Vacor-induced diabetic glomerulopathy. METHODS: Immunohistochemical analyses of type IV collagen, laminin, fibronectin and chondroitin sulfate proteoglycan were performed. A single dose of Vacor (molecular weight 272), 80 mg/kg, was administered to adult male Wistar rats by orogastric canule, and the animals were sacrificed at 0.5, 1, 3, 7, 14, 28 and 56 days after administration. RESULTS: Mild thickening of the glomerular basement membrane was evident 7 days after Vacor administration, and the width of the glomerular basement membrane was more than twice that of normal controls at 28 and 56 days. Significantly increased expressions of type IV collagen, laminin, fibronectin and neutral polysaccharide in the thickened glomerular basement membrane were noted 14 to 56 days after administration, and a mildly increased expression of chondroitin sulfate proteoglycan appeared between 3 to 7 days. CONCLUSION: These abnormally increased glomerular basement membrane components might be part of what causes diabetic nephropathy after Vacor administration.
Animal ; Basement Membrane/pathology ; Basement Membrane/metabolism ; Basement Membrane/drug effects ; Diabetic Nephropathies/pathology ; Diabetic Nephropathies/metabolism ; Diabetic Nephropathies/chemically induced* ; Extracellular Matrix Proteins/metabolism ; Kidney Glomerulus/pathology ; Kidney Glomerulus/metabolism ; Kidney Glomerulus/drug effects ; Male ; Phenylurea Compounds/toxicity* ; Proteochondroitin Sulfates/metabolism ; Rats ; Rats, Wistar