LR-90 prevents dyslipidaemia and diabetic nephropathy in the Zucker diabetic fatty rat.

摘要: Previous studies have shown that LR-90, a new inhibitor of AGE formation, prevented the development experimental type 1 diabetic nephropathy. In this study, we examined effects LR-90 in Zucker fatty (ZDF) rat, model 2 diabetes and metabolic syndrome, investigated mechanisms by which it may protect against renal injury. Male ZDF rats were treated without or with from age 13 to 40 weeks. Metabolic kidney functions histology evaluated. accumulation production receptor for (AGER) measured. Profibrotic growth factors, extracellular matrix proteins intracellular signalling pathways associated glomerular tubular damage also analysed. dramatically reduced plasma lipids rats, only modest on hyperglycaemia. Renal AGE, AGER lipid peroxidation all attenuated LR-90. significantly retarded increase albuminuria proteinuria. This was reduction glomerulosclerosis tubulointerstitial fibrosis, concomitant marked inhibition overproduction TGF-β1, connective tissue factor, fibronectin collagen IV. Additionally, downregulated activation key mitogen-activated protein kinases (MAPKs) nuclear factor kappa B (NF-κB) cortex. These results support our earlier renoprotective nephropathy provide further evidence an pleiotrophic effects, be beneficial prevention nephropathy, where multiple risk such as hyperglycaemia, dyslipidaemia, obesity, insulin resistance hypertension, contribute