ORAL-ADMINISTRATION OF METHYLGLYOXAL LEADS TO KIDNEY COLLAGEN ACCUMULATION IN THE MOUSE

Methylglyoxal (MG) is a physiological substrate of the glyoxalase syst em which is impaired in the diabetic state and implicated in the devel opment of diabetic complications. Like other reactive aldehydes in dia betes mellitus (DM) this carbonyl can bind to and modify proteins whic h may lead to changes of biochemical and biophysical properties of con nective 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 peri od 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 tak en for the determination of total kidney collagen, fluorescence, acid solubility of collagen and the right kidneys were used for the determi nation of glomerular basement membrane thickness. Total kidney collage n was significantly higher in the MG treated mice compared to control mice. Only about half the amount of collagen could be extracted from k idneys of MG treated animals indicating reduced solubility. Fluorescen ce in proteins from extracted kidneys of MG treated animals was about twice that of untreated animals. Glomerular basement membrane thicknes s was significantly higher in MG treated animals. Our findings indicat e that MG can increase glomerular basement membrane thickness and the suggested underlying mechanism may be decreased solubility by increase d cross linking as reflected by elevated protein fluorescence and decr eased acid salt extraction. The involvement of MG in the development o f diabetic complications postulated by others is herewith clearly supp orted by our findings.