The pesticide adjuvant, Toximul™, alters hepatic metabolism through effects on downstream targets of PPARα
| Autor: | Christopher J. Sinal, Philip D. Acott, Jacqueline Upham, John F. S. Crocker, Laurette Geldenhuys, Mary G. Murphy, Patrick A. O'Regan |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Male
Metabolite Peroxisome proliferator-activated receptor Pharmacology PPARα chemistry.chemical_compound Mice fluids and secretions 0302 clinical medicine Acyl-CoA oxidase Organic Chemicals Isomerases Enoyl-CoA Hydratase Pesticide adjuvant chemistry.chemical_classification Mice Knockout 0303 health sciences Oxidase test Mice Inbred ICR Fatty liver Fatty Acids Pesticide Synergists 3-Hydroxyacyl CoA Dehydrogenases Peroxisome Acetyl-CoA C-Acyltransferase PPARα-null mice Biochemistry Liver 030220 oncology & carcinogenesis Molecular Medicine Female Cytochrome P-450 CYP4A Oxidoreductases MRNA and protein expression Peroxisomal fatty-acid oxidation Biology Peroxisomal Bifunctional Enzyme 03 medical and health sciences Surface-Active Agents Multienzyme Complexes medicine Animals PPAR alpha Molecular Biology 030304 developmental biology Wild type Cyp4A medicine.disease Fatty Liver Mice Inbred C57BL chemistry Gene Expression Regulation 13. Climate action bacteria Acyl-CoA Oxidase Drug metabolism |
| Zdroj: | Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. 1772(9):1057-1064 |
| ISSN: | 0925-4439 |
| DOI: | 10.1016/j.bbadis.2007.06.003 |
| Popis: | Previous studies demonstrated that chronic dermal exposure to the pesticide adjuvant (surfactant), Toximul (Tox), has significant detrimental effects on hepatic lipid metabolism. This study demonstrated that young mice dermally exposed to Tox for 12 days have significant increases in expression of peroxisomal acyl-CoA oxidase (mRNA and protein), bifunctional enzyme (mRNA) and thiolase (mRNA), as well as the P450 oxidizing enzymes Cyp4A10 and Cyp4A14 (mRNA and protein). Tox produced a similar pattern of increases in wild type adult female mice but did not induce these responses in PPARalpha-null mice. These data support the hypothesis that Tox, a heterogeneous blend of nonionic and anionic surfactants, modulates hepatic metabolism at least in part through activation of PPARalpha. Notably, all three groups of Tox-treated mice had increased relative liver weights due to significant accumulation of lipid. This could be endogenous in nature and/or a component(s) of Tox or a metabolite thereof. The ability of Tox and other hydrocarbon pollutants to induce fatty liver despite being PPARalpha agonists indicates a novel consequence of exposure to this class of chemicals, and may provide a new understanding of fatty liver in populations with industrial exposure. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect