Activation of PXR, CAR and PPARα by pyrethroid pesticides and the effect of metabolism by rat liver microsomes
In this study, we used reporter gene assays in COS-1 cells to examine the activation of rat pregnane X receptor (PXR), rat constitutive androstane receptor (CAR) and rat peroxisome-proliferator activated receptor (PPAR)α by pyrethroid pesticides, and to understand the effects of metabolic modificati...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2019-09-01
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| Series: | Heliyon |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844019361262 |
| _version_ | 1818113478046515200 |
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| author | Chieri Fujino Yoko Watanabe Seigo Sanoh Hiroyuki Nakajima Naoto Uramaru Hiroyuki Kojima Kouichi Yoshinari Shigeru Ohta Shigeyuki Kitamura |
| author_facet | Chieri Fujino Yoko Watanabe Seigo Sanoh Hiroyuki Nakajima Naoto Uramaru Hiroyuki Kojima Kouichi Yoshinari Shigeru Ohta Shigeyuki Kitamura |
| author_sort | Chieri Fujino |
| collection | DOAJ |
| description | In this study, we used reporter gene assays in COS-1 cells to examine the activation of rat pregnane X receptor (PXR), rat constitutive androstane receptor (CAR) and rat peroxisome-proliferator activated receptor (PPAR)α by pyrethroid pesticides, and to understand the effects of metabolic modification on their activities. All eight pyrethroids tested in this study showed rat PXR agonistic activity; deltamethrin was the most potent, followed by cis-permethrin and cypermethrin. However, when the pyrethroids were incubated with rat liver microsomes, their rat PXR activities were decreased to various extents. Cis- and trans-permethrin showed weak rat CAR agonistic activity, while the other pyrethroids were inactive. However, fenvalerate showed dose-dependent inverse agonistic activity toward rat CAR, and this activity was reduced after metabolism. None of the pyrethroids showed rat PPARα agonistic activity, but a metabolite of cis-/trans-permethrin and phenothrin, 3-phenoxybenzoic acid, activated rat PPARα. Since PXR, CAR and PPARα regulate various xenobiotic/endobiotic-metabolizing enzymes, activation of these receptors by pyrethroids may result in endocrine disruption due to changes of hormone-metabolizing activities. |
| first_indexed | 2024-12-11T03:35:28Z |
| format | Article |
| id | doaj.art-3aa936cf2afd4a66a999cf55e88c40cd |
| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-12-11T03:35:28Z |
| publishDate | 2019-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj.art-3aa936cf2afd4a66a999cf55e88c40cd2022-12-22T01:22:15ZengElsevierHeliyon2405-84402019-09-0159e02466Activation of PXR, CAR and PPARα by pyrethroid pesticides and the effect of metabolism by rat liver microsomesChieri Fujino0Yoko Watanabe1Seigo Sanoh2Hiroyuki Nakajima3Naoto Uramaru4Hiroyuki Kojima5Kouichi Yoshinari6Shigeru Ohta7Shigeyuki Kitamura8Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8553, Japan; Nihon Pharmaceutical University, Komuro 10281, Ina-machi, Kitaadachi-gun, Saitama, 362-0806, Japan; Corresponding author.Nihon Pharmaceutical University, Komuro 10281, Ina-machi, Kitaadachi-gun, Saitama, 362-0806, JapanGraduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8553, JapanGraduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aramaki, Aoba, Aoba-ku, Sendai, 980-8578, Japan; School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka, 422-8526, JapanNihon Pharmaceutical University, Komuro 10281, Ina-machi, Kitaadachi-gun, Saitama, 362-0806, JapanSchool of Pharmaceutical Sciences, Health Sciences University of Hokkaido, 1757 Kanazawa, Ishikari-Tobetsu, Hokkaido, 061-0293, Japan; Hokkaido Institute of Public Health, Kita-19, Nishi-12, Kita-ku, Sapporo, 060-0819, JapanSchool of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka, 422-8526, JapanGraduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8553, Japan; Wakayama Medical University; 811-1 Kimiidera, Wakayama City, Wakayama, 641-8509, JapanNihon Pharmaceutical University, Komuro 10281, Ina-machi, Kitaadachi-gun, Saitama, 362-0806, JapanIn this study, we used reporter gene assays in COS-1 cells to examine the activation of rat pregnane X receptor (PXR), rat constitutive androstane receptor (CAR) and rat peroxisome-proliferator activated receptor (PPAR)α by pyrethroid pesticides, and to understand the effects of metabolic modification on their activities. All eight pyrethroids tested in this study showed rat PXR agonistic activity; deltamethrin was the most potent, followed by cis-permethrin and cypermethrin. However, when the pyrethroids were incubated with rat liver microsomes, their rat PXR activities were decreased to various extents. Cis- and trans-permethrin showed weak rat CAR agonistic activity, while the other pyrethroids were inactive. However, fenvalerate showed dose-dependent inverse agonistic activity toward rat CAR, and this activity was reduced after metabolism. None of the pyrethroids showed rat PPARα agonistic activity, but a metabolite of cis-/trans-permethrin and phenothrin, 3-phenoxybenzoic acid, activated rat PPARα. Since PXR, CAR and PPARα regulate various xenobiotic/endobiotic-metabolizing enzymes, activation of these receptors by pyrethroids may result in endocrine disruption due to changes of hormone-metabolizing activities.http://www.sciencedirect.com/science/article/pii/S2405844019361262Environmental healthEnvironmental sciencePesticideToxicologyCARLiver microsomes |
| spellingShingle | Chieri Fujino Yoko Watanabe Seigo Sanoh Hiroyuki Nakajima Naoto Uramaru Hiroyuki Kojima Kouichi Yoshinari Shigeru Ohta Shigeyuki Kitamura Activation of PXR, CAR and PPARα by pyrethroid pesticides and the effect of metabolism by rat liver microsomes Heliyon Environmental health Environmental science Pesticide Toxicology CAR Liver microsomes |
| title | Activation of PXR, CAR and PPARα by pyrethroid pesticides and the effect of metabolism by rat liver microsomes |
| title_full | Activation of PXR, CAR and PPARα by pyrethroid pesticides and the effect of metabolism by rat liver microsomes |
| title_fullStr | Activation of PXR, CAR and PPARα by pyrethroid pesticides and the effect of metabolism by rat liver microsomes |
| title_full_unstemmed | Activation of PXR, CAR and PPARα by pyrethroid pesticides and the effect of metabolism by rat liver microsomes |
| title_short | Activation of PXR, CAR and PPARα by pyrethroid pesticides and the effect of metabolism by rat liver microsomes |
| title_sort | activation of pxr car and pparα by pyrethroid pesticides and the effect of metabolism by rat liver microsomes |
| topic | Environmental health Environmental science Pesticide Toxicology CAR Liver microsomes |
| url | http://www.sciencedirect.com/science/article/pii/S2405844019361262 |
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