Probucol modulates Nrf2 function and ameliorates diabetic nephropathy in db/db mice

Background: In this study, we hypothesized that probucol can ameliorate diabetic nephropathy by inducing Nuclear factor erythroid 2-related factor 2 (Nrf2). We examined and compared the effects of probucol and pitavastatin on diabetic nephropathy in db/db mice. Methods: Db/db mice were fed with normal chow with or without 0.1% probucol or 0.005% pitavastatin for eight weeks. Blood and urine samples were collected before administration and four and eight weeks after the treatment. We also performed a histological analysis at the end of the study. Results: Probucol, but not pitavastatin, treatment significantly decreased both serum cholesterol and triglycerides by more than 50%. Probucol and pitavastatin treatment decreased 24 hour urinary albumin excretion and glomerular Nrf2 expression and produced a histological improvement of diabetic nephropathy. Conclusions: Our data demonstrates that probucol can ameliorate diabetic nephropathy through its cholesterol-lowering effect and possibly its modifing effects on Nrf2 function in diabetes.