Effects of pyrrolidine dithiocarbamate on high-fat diet-induced metabolic and renal alterations in rats.

Aims: We investigated the effects of the nuclear factor kappa B (NFkappaB) blocker pyrrolidine dithiocarbamate (PDTC) on high-fat diet (HFD)-induced metabolic and renal alterations in obese and lean Zucker rats (OZR and LZR, respectively).

Main Methods: Rats were fed a HFD resembling the typical "Western" diet or a regular diet (RD) and allowed free access to tap water or tap water containing PDTC (150 mg/kg body weight) for 10 weeks; rats were then sacrificed. Total ROS production rates were measured using electron paramagnetic resonance spectroscopy, and superoxide production was measured with lucigenin assay. Blood, plasma, and urine were analyzed. Semi-quantitative reverse transcriptase-polymerase chain reaction and electrophoretic mobility shift assay were conducted to assess NFkappaB mRNA levels and DNA binding activities, respectively; immunofluorescence was performed to assess protein levels.

Key Findings: OZR-HFD rats exhibited significantly higher levels of total renal cortical reactive oxygen species production, plasma lipids, insulin, C-reactive protein, blood urea nitrogen, creatinine, and urinary albumin excretion than all other groups (p<0.05); these changes were accompanied by a significant decrease in plasma high density lipoprotein levels (p<0.05). Gene expression levels of desmin, cytokine and oxidative stress genes were significantly higher in the renal cortical tissues of OZR-HFD; NFkappaB p65 DNA binding activity was also significantly higher in these animals. PDTC attenuated these changes.

Significance: Our data suggest that NFkappaB blockade may prove beneficial in treating the nephropathy often associated with metabolic syndrome.