A Biologically Based Dose-Response Model for Dietary Iodide and the Hypothalamic-Pituitary-Thyroid Axis in the Adult Rat: Evaluation of Iodide Deficiency

McLanahan, Eva D.; Andersen, Melvin E.; Fisher, Jeffrey W.

doi:10.1093/toxsci/kfm312

Cited by 42 publications

(48 citation statements)

References 62 publications

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“…Furthermore, rats are more convenient for consecutive blood sampling. As a consequence, rats were widely used in other studies on the thyroid [19][20][21][22] . In this study, we successfully collected sufficient blood samples from each rat by subclavian venous puncture instead of other, more invasive or even fatal methods at the end of the 12th, 18th and 24th weeks, and, therefore, greatly avoided interindividual variation.…”

Section: Discussionmentioning

confidence: 99%

Dietary high-fat lard intake induces thyroid dysfunction and abnormal morphology in rats

et al. 2014

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Aim: Excess dietary fat intake can induce lipotoxicity in non-adipose tissues. The aim of this study was to observe the effects of dietary high-fat lard intake on thyroid in rats. Methods: Male Sprague-Dawley rats were fed a high-fat lard diet for 24 weeks, and then the rats were fed a normal control diet (acute dietary modification) or the high-fat lard diet for another 6 weeks. The serum lipid profile, total thyroxine (TT4), free thyroxine (FT4) and thyrotropin (TSH) levels were determined at the 12, 18, 24 and 30 weeks. High-frequency ultrasound scanning of the thyroid glands was performed at the 24 or 30 weeks. After the rats were sacrificed, the thyroid glands were collected for histological and immunohistochemical analyses. Results: The high-fat lard diet significantly increased triglyceride levels in both the serum and thyroid, and decreased serum TT4 and FT4 levels in parallel with elevated serum TSH levels. Ultrasonic imaging revealed enlarged thyroid glands with lowered echotexture and relatively heterogeneous features in the high-fat lard fed rats. The thyroid glands from the high-fat lard fed rats exhibited enlarged follicle cavities and flattened follicular epithelial cells under light microscopy, and dilated endoplasmic reticulum cisternae, twisted nuclei, fewer microvilli and secretory vesicles under transmission electron microscopy. Furthermore, the thyroid glands from the highfat lard fed rats showed markedly low levels of thyroid hormone synthesis-related proteins TTF-1 and NIS. Acute dietary modification by withdrawal of the high-fat lard diet for 6 weeks failed to ameliorate the high-fat lard diet-induced thyroid changes. Conclusion: Dietary high-fat lard intake induces significant thyroid dysfunction and abnormal morphology in rats, which can not be corrected by short-term dietary modification.

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Section: Discussionmentioning

confidence: 99%

Dietary high-fat lard intake induces thyroid dysfunction and abnormal morphology in rats

et al. 2014

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“…Iodide ions excreted in urine is the result of metabolic processing of thyroid hormones or due to an excess in plasma concentration after an increase in oral iodine uptake (43). It was reported that about 95% of the daily iodide intake in rats was excreted in urine (11). However, this percentage can change significantly in case of iodide deficiency.…”

Section: Discussionmentioning

confidence: 99%

“…In fact, thyroid hormones are responsible for the normal development and regulation of brain, neurons, and processes that involve cerebral functions (10). A unique and specific mechanism that regulates thyroid hormones is the hypothalamic-pituitary-thyroid (HPT) axis which, as the name indicates, incorporate the hypothalamus, the pituitary gland, and the thyroid gland into forming a loop mechanism that keeps the concentration of these hormones at normal levels (11). This mechanism is initiated with the detection of low levels of thyroid hormones by the hypothalamus.…”

Section: Introductionmentioning

confidence: 99%

In Vivo Evaluation of Transdermal Iodide Microemulsion for Treating Iodine Deficiency Using Sprague Dawley Rats

et al. 2015

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ABSTRACT. The objective of this study was to evaluate the transdermal efficiency of iodide microemulsion in treating iodine deficiency using rats as an animal model. Animals were fed either iodine-deficient diet (20 μg/kg iodide) or control diet (200 μg/kg iodide) over a 17-month period. At month 14, iodide microemulsion was applied topically in iodine-deficient group and physiological evaluations of thyroid gland functions were characterized by monitoring the thyroid hormones (T 3 , T 4 ), thyroidstimulating hormone (TSH), iodide ion excretion in urine, and the overall rat body weights in both groups. Moreover, morphological evaluations of thyroid gland before and after treatment were performed by ultrasound imaging and through histological assessment. Prior to microemulsion treatment, the levels of T 3 , T 4 , and TSH in iodine-deficient group were statistically significant as compared to that in the control group. The levels of T 3 and T 4 increased while TSH level decreased significantly in iodine-deficient group within the first 4 weeks of treatment. After treatment, iodide concentration in urine increased significantly. There was no statistical difference in weight between the two groups. Ultrasound imaging and histological evaluations showed evidence of hyperplasia in iodine-deficient group. Topical iodide microemulsion has shown a promising potential as a novel delivery system to treat iodine deficiency.

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“…The hypothalamic-pituitary-thyroid (HPT) axis controls many physiologic functions, including metabolism, development, and reproduction. A biologically based dose-response (BBDR) model for adult rats includes submodels for dietary iodide, thyroid-stimulating hormone (TSH), and the thyroid hormones thyroxine (T4) and 3,5,3′- triiodothyronine (T3) [27, 28]. The independently developed individual submodels were linked together to form the endogeneous BBDR-HPT axis model.…”

Section: A Biologically Based Dose-response (Bbdr) Model Of Hypothmentioning

confidence: 99%

Application of Physiologically Based Pharmacokinetic Models in Chemical Risk Assessment

Mumtaz

Fisher

Blount

et al. 2012

Journal of Toxicology

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Post-exposure risk assessment of chemical and environmental stressors is a public health challenge. Linking exposure to health outcomes is a 4-step process: exposure assessment, hazard identification, dose response assessment, and risk characterization. This process is increasingly adopting “in silico” tools such as physiologically based pharmacokinetic (PBPK) models to fine-tune exposure assessments and determine internal doses in target organs/tissues. Many excellent PBPK models have been developed. But most, because of their scientific sophistication, have found limited field application—health assessors rarely use them. Over the years, government agencies, stakeholders/partners, and the scientific community have attempted to use these models or their underlying principles in combination with other practical procedures. During the past two decades, through cooperative agreements and contracts at several research and higher education institutions, ATSDR funded translational research has encouraged the use of various types of models. Such collaborative efforts have led to the development and use of transparent and user-friendly models. The “human PBPK model toolkit” is one such project. While not necessarily state of the art, this toolkit is sufficiently accurate for screening purposes. Highlighted in this paper are some selected examples of environmental and occupational exposure assessments of chemicals and their mixtures.

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A Biologically Based Dose-Response Model for Dietary Iodide and the Hypothalamic-Pituitary-Thyroid Axis in the Adult Rat: Evaluation of Iodide Deficiency

Cited by 42 publications

References 62 publications

Dietary high-fat lard intake induces thyroid dysfunction and abnormal morphology in rats

Dietary high-fat lard intake induces thyroid dysfunction and abnormal morphology in rats

In Vivo Evaluation of Transdermal Iodide Microemulsion for Treating Iodine Deficiency Using Sprague Dawley Rats

Application of Physiologically Based Pharmacokinetic Models in Chemical Risk Assessment

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