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.