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

Abstract

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.