کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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2571980 | 1128662 | 2006 | 10 صفحه PDF | دانلود رایگان |
Peroxisome proliferator-activated receptors (PPARs) are ligand-dependent transcription factors and key regulators of lipid metabolism and cell differentiation. However, there have been few studies reporting on a variety of environmental chemicals, which may interact with these receptors. In the present study, we characterized mouse PPARα and PPARγ agonistic activities of 200 pesticides (29 organochlorines, 11 diphenyl ethers, 56 organophosphorus pesticides, 12 pyrethroids, 22 carbamates, 11 acid amides, 7 triazines, 8 ureas and 44 others) by in vitro reporter gene assays using CV-1 monkey kidney cells. Three of the 200 pesticides, diclofop-methyl, pyrethrins and imazalil, which have different chemical structures, showed PPARα-mediated transcriptional activities in a dose-dependent manner. On the other hand, none of the 200 pesticides showed PPARγ agonistic activity at concentrations ≤ 10− 5 M. To investigate the in vivo effects of diclofop-methyl, pyrethrins and imazalil, we examined the gene expression of PPARα-inducible cytochrome P450 4As (CYP4As) in the liver of female mice intraperitoneally injected with these compounds (≤ 300 mg/kg). RT-PCR revealed significantly high induction levels of CYP4A10 and CYP4A14 mRNAs in diclofop-methyl- and pyrethrins-treated mice, whereas imazalil induced almost no gene expressions of CYP4As. In particular, diclofop-methyl induced as high levels of CYP4A mRNAs as WY-14643, a potent PPARα agonist. Thus, most of the 200 pesticides tested do not activate PPARα or PPARγ in in vitro assays, but only diclofop-methyl and pyrethrins induce PPARα agonistic activity in vivo as well as in vitro.
Journal: Toxicology and Applied Pharmacology - Volume 217, Issue 3, 15 December 2006, Pages 235–244