Pioglitazone, extract of compound Danshen dripping pill, and quercetin ameliorate diabetic nephropathy in diabetic rats.

BACKGROUND

Oxidative stress appears to play a role in the pathogenesis of diabetes mellitus (DM), and disruption of the ubiquitin-proteasome system may underlie these pathological changes. We tested the effect of pioglitazone (PIO), an extract of Danshen dripping pill (DSP), and quercetin (QUE) on the pathogenesis of DM in a rat model.

METHODS

Male Sprague Dawley rats were maintained in a normal control (NC) group or given a modified diet and streptozotocin (STZ) to induce DM. After STZ treatment, rats were given intragastric placebo, PIO, DSP, or QUE for 8 weeks. At the end of the treatment period, serum and urine chemistry, renal hypertrophy, renal histopathology, and renal expression of ubiquitin and nuclear factor (NF)-κB p65 were analyzed.

RESULTS

DM rats had altered body and kidney weight, altered serum and urine chemistry, increased accumulation of glomerular extracellular matrix (ECM), and increased renal expression of ubiquitin and NF-κB p65, indicating successful establishment of our DM model. Treatment with PIO, DSP, or QUE significantly ameliorated these pathological changes, although treated rats still had some symptoms of DM.

CONCLUSION

DM rats have increased expression of ubiquitin and NF-κB p65 in their renal tubules and glomeruli. PIO, DSP, and QUE ameliorated the pathological changes associated with DM and also reduced the renal expression of ubiquitin and NF-κB p65. These agents may provide protection from renal pathology associated with DM due to their anti-oxidant effects.