Effects of pyrrolidine dithiocarbamate on high-fat diet-induced metabolic and renal alterations in rats.
Effects of pyrrolidine dithiocarbamate on high-fat diet-induced metabolic and renal alterations in rats.
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DOI：
10.1016/j.lfs.2009.06.019
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发表时间：
2009-08-26
期刊：
影响因子：
6.1
通讯作者：
Francis, Joseph
中科院分区：
文献类型：
--
作者：
Ebenezer, Philip J.;Mariappan, Nithya;Elks, Carrie M.;Haque, Masudul;Soltani, Zohreh;Reisin, Efrain;Francis, Joseph
我们研究了核因子κ B（NFκB）阻断剂吡咯烷二硫代氨基甲酸酯（PDTC）对肥胖和瘦Zucker大鼠（分别为OZR和LZR）高脂饮食（HFD）诱导的代谢和肾脏改变的影响。给大鼠喂食类似于典型“西方”饮食或常规饮食（RD）的HFD，并允许自由获取自来水或含有PDTC（150 mg/kg体重）的自来水10周;然后处死大鼠。总的ROS生产率测定使用电子顺磁共振光谱，超氧化物的生产与光泽精测定。分析血液、血浆和尿液。分别采用半定量逆转录聚合酶链反应和电泳迁移率变动分析评估NFκB mRNA水平和DNA结合活性;免疫荧光法评估蛋白水平。OZR-HFD大鼠的总肾皮质活性氧产生、血浆脂质、胰岛素、C-反应蛋白、血尿素氮、肌酐和尿白蛋白排泄水平显著高于所有其他组（p<0.05）;这些变化伴随着血浆高密度脂蛋白水平的显著降低（p<0.05）。结蛋白、细胞因子和氧化应激基因的基因表达水平在OZR-HFD的肾皮质组织中显著升高; NFκB p65 DNA结合活性在这些动物中也显著升高。PDTC减弱了这些变化。我们的数据表明，NFκB阻断可能被证明是有益的，在治疗肾病往往与代谢综合征。
We investigated the effects of the nuclear factor kappa B (NFκB) blocker pyrrolidine dithiocarbamate (PDTC) on high-fat diet (HFD)-induced metabolic and renal alterations in obese and lean Zucker rats (OZR and LZR, respectively). 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 NFκB mRNA levels and DNA binding activities, respectively; immunofluorescence was performed to assess protein levels. 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; NFκB p65 DNA binding activity was also significantly higher in these animals. PDTC attenuated these changes. Our data suggest that NFκB blockade may prove beneficial in treating the nephropathy often associated with metabolic syndrome.
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DOI：
10.1097/01.asn.0000135971.88164.2c
发表时间：
2004-09-01
影响因子：
13.6
作者：
Chander, PN;Gealekman, O;Goligorsky, MS
通讯作者：
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DOI：
10.1152/ajpheart.00286.2007
发表时间：
2007-07-01
影响因子：
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Uusitupa, M.
影响因子：
19.6
作者：
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影响因子：
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作者：
Khaleduzzaman, Mohammed;Francis, Joseph;Peterson, Karin E.
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