Protective effect of unsaturated fatty acids against glycation-induced structural and functional alteration of albumin: Perspectives on diabetic nephropathy.

Diabetic nephropathy (DN) is the leading cause of end-stage renal disease, and the protein glycation pathway has a major role in DN pathogenesis. Accumulation of advanced glycation end products (AGEs) upregulates the Receptor for Advanced Glycation End products (RAGE)-NF-κB pathway, leading to elevated oxidative stress and inflammation. The present study aims to shed light on the anti-glycation mechanism of unsaturated fatty acids (UFAs), such as oleic acid (OA), linoleic acid (LA), and docosahexaenoic acid (DHA), on glycated human serum albumin (G. HSA) in an in vitro setup using multispectroscopic techniques and renal cellular studies with HEK-293 cells. HSA (10 mg/mL) and methylglyoxal (55 mM) were incubated for 8 days at 37 °C in the presence of aminoguanidine and UFAs (200 μM). HSA's structural (fructosamine, free amino group, CD, FTIR), functional (ABTS, thermogravimetric analysis, isothermal titration calorimetry) and aggregation markers (FE-SEM, β -amyloid content) were studied. HEK-293 cells were treated with HSA, glycated HSA (400 μg/mL), OA, LA, DHA (200 μM) and RAGE antagonist (FPS-ZMI, 150 nM) separately for examining glycation markers, antioxidant markers (superoxide dismutase, catalase activity and glutathione) and glycation detoxification enzymes (Glyoxalase I and II). Gene expression of RAGE-NF-κB signalling and mitochondrial dysfunction was studied using RT-qPCR. DHA and LA prevented glycation-induced structural changes that aid in maintaining the structural modifications of HSA against glycation. The LA treatments have shown promising results in inhibiting cellular glycation and oxidative stress. These results comprehensively demonstrate the anti-glycation potential of UFAs in attenuating RAGE-NF-κB signalling and oxidative and mitochondrial stress in renal cells, and they warrant further exploration as a treatment modality for DN.