Oral administration of methylglyoxal leads to kidney collagen accumulation in the mouse

Methylglyoxal (MG) is a physiological substrate of the glyoxalase system which is impaired in the diabetic state and implicated in the development of diabetic complications. Like other reactive aldehydes in diabetes mellitus (DM) this carbonyl can bind to and modify proteins which may lead to changes of biochemical and biophysical properties of connective tissue proteins, a hallmark of diabetes mellitus. As previous studies on MG effects were confounded by other aldehydes found in DM, we decided to administer MG to 10 healthy, female OF-1 mice for a period of five months, at a level of 50 mg/kg body weight per day using 10 healthy untreated litter mates as controls. The left kidneys were taken for the determination of total kidney collagen, fluorescence, acid solubility of collagen and the right kidneys were used for the determination of glomerular basement membrane thickness. Total kidney collagen was significantly higher in the MG treated mice compared to control mice. Only about half the amount of collagen could be extracted from kidneys of MG treated animals indicating reduced solubility. Fluorescence in proteins from extracted kidneys of MG treated animals was about twice that of untreated animals. Glomerular basement membrane thickness was significantly higher in MG treated animals. Our findings indicate that MG can increase glomerular basement membrane thickness and the suggested underlying mechanism may be decreased solubility by increased cross linking as reflected by elevated protein fluorescence and decreased acid salt extraction. The involvement of MG in the development of diabetic complications postulated by others is herewith clearly supported by our findings.