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Effects of tris(1,3-dichloro-2-propyl)phosphate on pathomorphology and gene/protein expression related to thyroid disruption in rats
- Source :
- Toxicology Research. 5:921-930
- Publication Year :
- 2016
- Publisher :
- Oxford University Press (OUP), 2016.
-
Abstract
- Previous studies demonstrated that tris(1,3-dichloro-2-propyl)phosphate (TDCIPP) caused adverse effects on thyroid hormone (TH) imbalance in aquatic and avian organisms. This study focused on the effects of TDCIPP on thyroid function and hormone homeostasis in mammals. Pubertal female Sprague-Dawley rats were orally administered 50, 100, or 250 mg per kg per d of TDCIPP from postnatal day (PND) 22 to PND42 for 21 days. The serum triiodothyronine (T3) levels increased significantly at 250 mg per kg per d of TDCIPP. There were no significant differences in the body weight, serum thyroxine (T4) and free thyroxine (FT4) levels between the control and TDCIPP treated groups. There were significant dose-dependent increases in the mRNA and protein expression levels of genes related to drug metabolism (cytochrome-p450-3A1, CYP3A1) and TH clearance (udp-glucuronosyltransferase-1A6, UGT1A6) in the liver. Treatment with TDCIPP increased hepatic type 1 deiodinase (DIO1) mRNA at 250 mg per kg per d but down-regulated hepatic TH receptor beta (TRĪ²) mRNA expression. In addition, TDCIPP exposure induced slight thyroid follicular hyperplasia, and several genes involved in TH biosynthesis (NIS, TPO, Tg) were altered at 100 and 250 mg per kg per d of TDCIPP. Nevertheless, serum thyroid stimulating hormone (TSH) levels and the receptor (TSHr) mRNA significantly decreased at only the low dose group. Based on these results, we certified that TDCIPP disturbs the normal bioprocess on TH synthesis, biotransformation or clearance, and hepatic detoxification of pubertal female SD rats, causing thyroid function disorder.
- Subjects :
- 0301 basic medicine
endocrine system
medicine.medical_specialty
endocrine system diseases
Health, Toxicology and Mutagenesis
Tris(1,3-dichloro-2-propyl)phosphate
010501 environmental sciences
Biology
Toxicology
01 natural sciences
03 medical and health sciences
chemistry.chemical_compound
Thyroid-stimulating hormone
Internal medicine
medicine
Receptor
0105 earth and related environmental sciences
Triiodothyronine
Thyroid
Chemistry
030104 developmental biology
medicine.anatomical_structure
Endocrinology
chemistry
Thyroid function
Drug metabolism
Hormone
Subjects
Details
- ISSN :
- 20454538 and 2045452X
- Volume :
- 5
- Database :
- OpenAIRE
- Journal :
- Toxicology Research
- Accession number :
- edsair.doi.dedup.....5bbca7cd298ae0ae963b4293f4377181