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In vivo Characterization of Endocrine Disrupting Chemical Effects via Thyroid Hormone Action Indicator Mouse
Published on: October 6, 2023
The decrease in level of serum thyroxine by 2,2',4,5,5'-pentachlorobiphenyl in rats and mice: no correlation with
Yoshihisa Kato1, Koichi Haraguchi, Tomoaki Yamazaki
1School of Pharmaceutical Sciences, University of Shizuoka, hizuoka, Japan. kato@ys7.u-shizuoka-ken.ac.jp
Abstract:
A relationship between formation of methylsulfonyl (MeSO2) metabolites of 2,2',4,5,5'-pentachlorobiphenyl (PentaCB) and decrease in serum thyroxine (T4) level was examined in the rats and mice after a single i.p. injection of PentaCB (342 micromol/kg body weight). In either rats or mice, levels of the 3- and 4-MeSO2 metabolites of PentaCB in the liver and feces increased in a time-dependent fashion up to 8 days after PentaCB-treatment. However, there was a marked difference between rats and mice in the amount of the metabolites formed, and the cumulative amount of the either MeSO2 metabolite for 8 days after PentaCB treatment in the liver was 4 to 15 times higher in mice than in rats. On the other hand, a 40 to 60% decrease in level of serum total T4 occurred in both rats and mice at 1 day after PentaCB treatment, and the decrease was retained up to 8 days after PentaCB treatment. Thus, there was a marked difference between rats and mice in the formation of MeSO2 metabolites from PentaCB but not a significant difference between rats and mice in PentaCB-induced decrease in the level of serum total T4, indicating that PentaCB-induced decrease in the level of serum total T4 is not necessarily dependent on the MeSO2 metabolites formed.
Insights
The formation of methylsulfonyl (MeSO2) metabolites from 2,2
Area of Science:
- Environmental Toxicology
- Metabolomics
- Endocrinology
Background:
- Polychlorinated biphenyls (PCBs) are persistent environmental pollutants.
- PCBs can be metabolized into various compounds, including methylsulfonyl (MeSO2) metabolites.
- Thyroxine (T4) is a critical thyroid hormone involved in metabolism and development.
Purpose of the Study:
- To investigate the relationship between the formation of methylsulfonyl (MeSO2) metabolites of 2,2',4,5,5'-pentachlorobiphenyl (PentaCB) and the decrease in serum thyroxine (T4) levels.
- To compare the formation of MeSO2 metabolites and the impact on T4 levels in rats and mice following PentaCB exposure.
Main Methods:
- Rats and mice were administered a single intraperitoneal injection of PentaCB.
- Levels of MeSO2 metabolites in the liver and feces were measured over 8 days.
- Serum total T4 levels were monitored at 1 and 8 days post-injection.
Main Results:
- MeSO2 metabolite levels in the liver and feces increased time-dependently in both species.
- Mice formed significantly higher cumulative amounts of MeSO2 metabolites (4-15 times more) than rats.
- Both rats and mice exhibited a 40-60% decrease in serum total T4 by day 1, sustained up to day 8.
Conclusions:
- PentaCB exposure leads to a significant decrease in serum T4 levels in both rats and mice.
- Despite marked differences in MeSO2 metabolite formation between rats and mice, the reduction in serum T4 was similar.
- These findings suggest that PentaCB-induced decreases in serum T4 are not solely dependent on the formation of MeSO2 metabolites.
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