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Thyroid Dysfunction Induced by Fungicide Famoxadone Exposure Contributes to Nonalcoholic Fatty Liver Disease in Male Mice: In Vivo, In Vitro, and In Silico Studies
journal contribution
posted on 2023-09-26, 04:29 authored by Shouchun Xiao, Jingna Cui, Aisong Chen, Haonan Hou, Jianing Yao, Yue Cao, Yaofeng Fang, Xueke Liu, Zhiqiang Zhou, Donghui Liu, Peng WangThyroid
dysfunction has become a serious public health
problem,
which is considered a trigger of nonalcoholic fatty liver disease
(NAFLD). Pesticide exposure could contribute to thyroid dysfunction
and NAFLD, but the relationship between these factors remains unclear.
In this study, the effects of subchronic famoxadone exposure on thyroid
and liver at no observed adverse effect level (NOEL) related concentrations
were investigated using in vivo, in vitro, and in silico models. Famoxadone caused hepatic
steatosis, lipid metabolism disorder, and liver oxidative stress and
induced NAFLD in male mice. The suppression of hepatic fatty acid
β-oxidation was the key factor of NAFLD, which was highly associated
with hypothalamic–pituitary–thyroid (HPT) axis hormones
disorder. Famoxadone disrupted thyroid hormone biosynthesis by causing
thyroid follicle aberrations and abnormal HPT axis-related gene expression. In vitro studies confirmed that famoxadone inhibited the
transport of thyroxine (T4) into hepatocytes and the conversion of
T4 to triiodothyronine (T3). In silico studies verified
that famoxadone interfered with the binding of thyroid hormones to
proteins mediating thyroid hormone transport, conversion, and activation.
This study comprehensively reported the association between NAFLD
and thyroid dysfunction caused by famoxadone, providing new perspectives
for the health risk evaluation of pesticides with a similar structure
in mammals.
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providing new perspectiveslipid metabolism disorderhealth risk evaluationfactors remains unclearrelated gene expressionaxis hormones disorderthyroid dysfunction causedsubchronic famoxadone exposurestudy comprehensively reportedliver oxidative stressabnormal hpt axisthyroid dysfunction inducedstudies thyroid dysfunctionthyroid dysfunctionthyroid hormonesrelated concentrationsstudies verifiedstudies confirmedinduced nafldvivo vitro t3 ).similar structuresilico male micekey factorinvestigated usinghighly associatedfamoxadone interferedfamoxadone inhibited