TY - JOUR
T1 - Activation of Hepatic NF-κB by the Herbicide Dicamba (2-methoxy-3,6-dichlorobenzoic acid) in Female and Male Rats
AU - Espandiari, P.
AU - Ludewig, G.
AU - Glauert, H. P.
AU - Robertson, L. W.
PY - 1998
Y1 - 1998
N2 - Nuclear factor-KB is a transcription factor that is activated in many different cell types by pathologic stimuli, such as reactive oxygen intermediates. One class of hepatocarcinogens, the peroxisome proliferators, may produce reactive oxygen intermediates, and one potent peroxisome proliferator, ciprofibrate, was recently reported to activate nuclear factor-κB. In this study, we investigated whether Dicamba, a broad leaf herbicide and peroxisome proliferator, could activate nuclear factor-κB in the livers of rats. Female and male Sprague Dawley rats (n = 4) were fed diets containing either 0,1, or 3% Dicamba or 0.01% ciprofibrate for 7 days. As expected, the potent peroxisome proliferator, ciprofibrate, significantly increased fatty acyl CoA oxidase, peroxisomal β-oxidation, and catalase activities in male rats and, except for catalase, also in female rats. Dicamba significantly increased peroxisomal fatty acyl CoA oxidase, peroxisomal β-oxidation, and catalase activities, but decreased the activity of the cytosolic antioxidant enzyme, Se-dependent glutathione peroxidase, in both female and male rats. Dicamba increased nuclear factor-κB binding in the nuclear protein of livers from male rats fed both the 1 and 3% Dicamba diets. However, the highest binding was seen in nuclear protein from female rats fed 3% Dicamba. Both supershift and cold competition assays confirmed that this DNA binding activity was specific for nuclear factor-κB. Our results in this study suggest that the herbicide and peroxisome proliferator Dicamba has the ability to activate nuclear factor-κB.
AB - Nuclear factor-KB is a transcription factor that is activated in many different cell types by pathologic stimuli, such as reactive oxygen intermediates. One class of hepatocarcinogens, the peroxisome proliferators, may produce reactive oxygen intermediates, and one potent peroxisome proliferator, ciprofibrate, was recently reported to activate nuclear factor-κB. In this study, we investigated whether Dicamba, a broad leaf herbicide and peroxisome proliferator, could activate nuclear factor-κB in the livers of rats. Female and male Sprague Dawley rats (n = 4) were fed diets containing either 0,1, or 3% Dicamba or 0.01% ciprofibrate for 7 days. As expected, the potent peroxisome proliferator, ciprofibrate, significantly increased fatty acyl CoA oxidase, peroxisomal β-oxidation, and catalase activities in male rats and, except for catalase, also in female rats. Dicamba significantly increased peroxisomal fatty acyl CoA oxidase, peroxisomal β-oxidation, and catalase activities, but decreased the activity of the cytosolic antioxidant enzyme, Se-dependent glutathione peroxidase, in both female and male rats. Dicamba increased nuclear factor-κB binding in the nuclear protein of livers from male rats fed both the 1 and 3% Dicamba diets. However, the highest binding was seen in nuclear protein from female rats fed 3% Dicamba. Both supershift and cold competition assays confirmed that this DNA binding activity was specific for nuclear factor-κB. Our results in this study suggest that the herbicide and peroxisome proliferator Dicamba has the ability to activate nuclear factor-κB.
KW - Dicamba
KW - NF-κB
KW - Oxidative Stress
KW - Peroxisome Proliferator
UR - http://www.scopus.com/inward/record.url?scp=0031610078&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0031610078&partnerID=8YFLogxK
U2 - 10.1002/(SICI)1099-0461(1998)12:6<339::AID-JBT3>3.0.CO;2-N
DO - 10.1002/(SICI)1099-0461(1998)12:6<339::AID-JBT3>3.0.CO;2-N
M3 - Article
C2 - 9736482
AN - SCOPUS:0031610078
SN - 1095-6670
VL - 12
SP - 339
EP - 344
JO - Journal of Biochemical and Molecular Toxicology
JF - Journal of Biochemical and Molecular Toxicology
IS - 6
ER -