In vitro screening of 200 pesticides for agonistic activity via mouse peroxisome proliferator-activated receptor (PPAR){alpha} and PPAR{gamma} and quantitative analysis of in vivo induction pathway

Journal Article · Fri Dec 15 04:00:00 EST 2006 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/j.taap.2006.08.011· OSTI ID:20850497

Takeuchi, Shinji ^[1]; Matsuda, Tadashi ^[2]; Kobayashi, Satoshi ^[1]; Takahashi, Tetsuo ^[1]; Kojima, Hiroyuki ^[1]

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1. Hokkaido Institute of Public Health, Kita-19, Nishi-12, Kita-ku, Sapporo 060-0819 (Japan)
2. Department of Immunology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812 (Japan)

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 PPAR{alpha} and PPAR{gamma} 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 PPAR{alpha}-mediated transcriptional activities in a dose-dependent manner. On the other hand, none of the 200 pesticides showed PPAR{gamma} agonistic activity at concentrations {<=} 10{sup -5} M. To investigate the in vivo effects of diclofop-methyl, pyrethrins and imazalil, we examined the gene expression of PPAR{alpha}-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 PPAR{alpha} agonist. Thus, most of the 200 pesticides tested do not activate PPAR{alpha} or PPAR{gamma} in in vitro assays, but only diclofop-methyl and pyrethrins induce PPAR{alpha} agonistic activity in vivo as well as in vitro.

• OSTI ID: 20850497
• Journal Information: Toxicology and Applied Pharmacology, Journal Name: Toxicology and Applied Pharmacology Journal Issue: 3 Vol. 217; ISSN TXAPA9; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
CARBAMATES
CELL DIFFERENTIATION
GENES
IN VITRO
IN VIVO
KIDNEYS
LIGANDS
LIPIDS
LIVER
METABOLISM
MICE
MONKEYS
PESTICIDES
PHENYL ETHER
POLYMERASE CHAIN REACTION
RECEPTORS
TRANSCRIPTION FACTORS
TRIAZINES
UREA