Pyruvate is an
endogenous antioxidant and anti-inflammatory substance. The present study was implemented to investigate the protective effect of
ethyl pyruvate (EP) against the development and progression of
diabetic nephropathy in an in vivo and in vitro model. Diabetic rats were prepared by injecting
streptozotocin (65 mg/kg). Those that developed diabetes after 72 h were treated with EP (40 mg/kg) intraperitoneally. Diabetic rats without
pyruvate treatment and nondiabetic rats were used for control. As an in vitro experiment, rat mesangial cells cultured primarily from Sprague-Dawley rats were treated in high-
glucose (HG; 50 mM) or normal-
glucose (NG; 5 mM) conditions and with or without
pyruvate.
Pyruvate-treated diabetic rats exhibited decreased
albuminuria and attenuated
NADPH-dependent
reactive oxygen species generation. Immunohistochemistry showed reduced
laminin,
type IV collagen, and
fibronectin deposition in the glomeruli compared with nontreated diabetic rats. Parallel changes were shown in tissue
mRNA and
protein expression levels of
monocyte chemoattractant protein-1, transforming growth factor-β1,
laminin,
fibronectin, and
type IV collagen in the kidney. Concordantly, protective effects were also exhibited in the mesangial cell culture system. These findings suggest that
pyruvate protects against kidney injury via
NADPH oxidase inhibition. The present study established that activation of
NADPH oxidase plays a crucial role in diabetes-induced oxidative stress, glomerular
hypertrophy, and ECM molecule expression.
Pyruvate exhibited a renoprotective effect in the progression of experimental
diabetic nephropathy. Future research is warranted to investigate the protective mechanism of
pyruvate more specifically in relation to
NADPH oxidase in
diabetic nephropathy.