Fucoidan exerts protective effects against diabetic nephropathy related to spontaneous diabetes through the NF-κB signaling pathway in vivo and in vitro

Abstract

Fucoidan, an extract of the seaweed, Fucus vesiculosus, has been widely investigated for its antioxidant effects. However, to date and to the best of our knowledge, pathological studies on the effects of fucoidan against diabetic nephropathy (DN) related to spontaneous diabetes have not been carried out. DN is one of the most serious microvascular complications of diabetes. Therefore, in the present study, the effects of fucoidan against DN related to spontaneous diabetes were investigated in vitro and in vivo. Goto-Kakizaki (GK) rats were allowed free access to standard rat food with or without fucoidan for 13 weeks, and Wistar rats were used as controls. Fucoidan did not show any cytotoxicity on glomerular mesangial cells (GMCs) which were separated from rat kidneys. Fasting blood glucose levels were measured using a blood glucose meter, blood urea nitrogen (BUN) and serum creatinine (Cr) levels were measured using an automatic biochemistry analyzer and urine protein levels were measured using an ELISA kit. Collagen Ⅳ levels in the renal cortex were measured using an ELISA kit, and the expression levels of transforming growth factor-β1 (TGF-β1) and fibronectin (FN) in the renal cortex and GMCs, and nuclear factor-κB (NF-κB) in GMCs were determined by western blot analysis. Fasting blood glucose, BUN, serum Cr, urine protein and collagen Ⅳ levels, and the expression of TGF-β1 and FN, as well as NF-κB p65 nuclear translocation all significantly increased in the GK rats compared with the control Wistar rats. The increase in the fasting blood glucose, BUN, serum Cr, urine protein and collagen Ⅳ levels in the renal cortex was reversed in the GK rats which were orally administered fucoidan. The oral administration of fucoidan also decreased the expression of TGF-β1 and FN in the renal cortex and GMCs, as well as the nuclear translocation of NF-κB p65 in the GMCs. Taken together, the data from our in vitro and in vivo experiments indicate that fucoidan attenuates hyperglycemia and prevents or impedes the development of DN related to spontaneous diabetes by attenuating the activation of the NF-κB signaling pathway.