This study addressed the relationship of proinflammatory
cytokines and Nrf2-Keap1 system in
diabetic nephropathy. The experimental groups were control, diabetic, and diabetic treated with
mycophenolate mofetil (MMF). The renal function, proinflammatory and profibrotic
cytokines, oxidative stress, morphology, and
nephrin expression were assessed. Diabetic group showed impaired renal function in association with oxidative stress and decreased Nrf2 nuclear translocation. These results were associated with increased mesangial matrix index, interstitial
fibrosis, and increased
nephrin expression in cortex and urine excretion. Additionally, interleukin-1β,
IL-6, and transforming growth factor-β1 were increased in plasma and kidney. MMF treatment conserved renal function, prevented renal structural alterations, and partially prevented the proinflammatory and profibrotic
cytokines overexpression. Despite that MMF treatment induced
nephrin overexpression in renal tissue, preventing its urinary loss. MMF salutary effects were associated with a partial prevention of oxidative stress, increased Nrf2 nuclear translocation, and conservation of
antioxidant enzymes in renal tissue. In conclusion, our results confirm that
inflammation is a key factor in the progression of
diabetic nephropathy and suggest that treatment with MMF protects the kidney by an
antioxidant mechanism, possibly regulated at least in part by the Nrf2/Keap1 system, in addition to its well-known anti-inflammatory effects.