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


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.


RESULTS
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.


CONCLUSIONS
Our data suggest that NFkappaB blockade may prove beneficial in treating the nephropathy often associated with metabolic syndrome.
Ebenezer
Philip J
PJ
Department of Comparative Biomedical Sciences, Louisiana State University School of Veterinary Medicine, Baton Rouge, LA 70803, USA.
Mariappan
Nithya
N
Elks
Carrie M
CM
Haque
Masudul
M
Soltani
Zohreh
Z
Reisin
Efrain
E
Francis
Joseph
J
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D004032:Diet; D004041:Dietary Fats; D005786:Gene Expression Regulation / Q000187:drug effects; D007668:Kidney / Q000187:drug effects*; D008055:Lipids / Q000097:blood; D051379:Mice; D009929:Organ Size / Q000187:drug effects; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D011924:Rats, Zucker; D017382:Reactive Oxygen Species / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013859:Thiocarbamates / Q000494:pharmacology*
D000975:Antioxidants; D004041:Dietary Fats; D008055:Lipids; D011759:Pyrrolidines; D017382:Reactive Oxygen Species; D013859:Thiocarbamates; C020972:pyrrolidine dithiocarbamic acid