Effects of α-lipoic acid on transforming growth factor β1–p38 mitogen-activated protein kinase–fibronectin pathway in diabetic nephropathy

In diabetic nephropathy, transforming growth factor β1 (TGFβ1) is related to p38 mitogen-activated protein kinase (MAPK) that induces production of fibronectin in mesangial cells. We investigated the effects of α-lipoic acid (ALA), a potent antioxidant, on proteinuria and TGFβ1–p38 MAPK–fibronectin pathway in diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats. After ALA treatment for 5 weeks in OLETF rats at 30 weeks of age, plasma malondialdehyde, urinary protein excretion, renal cortical TGFβ1, and fibronectin protein levels were decreased; and urinary protein excretion was positively correlated with renal cortical TGFβ1 and fibronectin protein levels. Phospho-form but not total-form levels as well as fold activations of each protein consisting of p38 MAPK pathway were also attenuated. These results suggest that ALA ameliorates proteinuria by attenuating expressions of TGFβ1 and fibronectin proteins, and these favorable effects are related to inhibition of phosphorylating activation of p38 MAPK pathway in renal cortex of OLETF rats.