Methimazole-induced hypothyroidism causes cellular damage in the spleen, heart, liver, lung and kidney

Cano-Europa, Edgar; Blas-Valdivia, Vanessa; Franco-Colín, Margarita; Gallardo-Casas, Carlos Angel; Ortiz-Butrón, Rocı́o

doi:10.1016/j.acthis.2009.07.004

Cited by 56 publications

(44 citation statements)

References 24 publications

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“…Various strategies have been used to promote hypothyroidism in animals, including surgical ablation of the thyroid gland [43], radio-thyroidectomy using isotopes [44], and through pharmacological approaches using anti-thyroid drugs such as MMI and propylthiouracil [31,45]. Administration of anti-thyroid drugs reversibly inhibits TH production.…”

Section: Discussionmentioning

confidence: 99%

Acute Treatment with T-Type Calcium Channel Enhancer SAK3 Reduces Cognitive Impairments Caused by Methimazole-Induced Hypothyroidism Via Activation of Cholinergic Signaling

Noreen¹,

Yabuki²,

Shinoda³

et al. 2018

Pharmacology

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Hypothyroidism is a common disorder that is associated with psychological disturbances such as dementia, depression, and psychomotor disorders. We recently found that chronic treatment with the T-type calcium channel enhancer SAK3 prevents the cholinergic neurodegeneration induced by a single intraperitoneal (i.p.) injection of methimazole (MMI; 75 mg/kg), thereby improving cognition. Here, we evaluated the acute effect of SAK3 on cognitive impairments and its mechanism of action following the induction of hypothyroidism. Hypothyroidism was induced by 2 injections of MMI (75 mg/kg, i.p.) administered once per week. Four weeks after the final MMI treatment, MMI-treated mice showed reduced serum thyroxine (T4) levels and cognitive impairments without depression-like behaviors. Although acute SAK3 (1.0 mg/kg, p.o.) administration failed to ameliorate the decreased T4 levels and histochemical destruction of the glomerular structure, acute SAK3 (1.0 mg/kg, p.o.) administration significantly reduced cognitive impairments in MMI-treated mice. Importantly, the α7 nicotinic acetylcholine receptor (nAChR)-selective inhibitor methyllycaconitine (MLA; 12 mg/kg, i.p.) and T-type calcium channel-specific blocker NNC 55–0396 (25 mg/kg, i.p.) antagonized the acute effect of SAK3 on memory deficits in MMI-treated mice. We also confirmed that acute SAK3 administration does not rescue reduced olfactory marker protein or choline acetyltransferase immunoreactivity levels in the olfactory bulb or medial septum. Taken together, these results suggest that SAK3 has the ability to improve the cognitive decline caused by hypothyroidism directly through activation of nAChR signaling and T-type calcium channels.

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Section: Discussionmentioning

confidence: 99%

Acute Treatment with T-Type Calcium Channel Enhancer SAK3 Reduces Cognitive Impairments Caused by Methimazole-Induced Hypothyroidism Via Activation of Cholinergic Signaling

Noreen¹,

Yabuki²,

Shinoda³

et al. 2018

Pharmacology

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“…While treatment of mice with antithyroid drugs in drinking water is a widely used approach to render mice hypothyroid, mice have to be treated throughout the experiment, a certain degree of variability remains due to differences in water intake and potential side effects of the drugs have to be taken into consideration [26,27]. Furthermore, as this approach typically relies on a combination of thioamides (methimazole or propylthiouracil) that have been shown to affect thyroidal NIS expression [28], as well as the NIS-specific inhibitor perchlorate to block thyroid hormone synthesis, the use of NIS as a reporter gene to study thyroid hormone action is limited in this setting.…”

Section: Discussionmentioning

confidence: 99%

Establishment of an Effective Radioiodide Thyroid Ablation Protocol in Mice

Schmohl¹,

Müller²,

Schwenk³

et al. 2015

Eur Thyroid J

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Due to the high variance in available protocols on iodide-131 (¹³¹I) ablation in rodents, we set out to establish an effective method to generate a thyroid-ablated mouse model that allows the application of the sodium iodide symporter (NIS) as a reporter gene without interference with thyroidal NIS. We tested a range of ¹³¹I doses with and without prestimulation of thyroidal radioiodide uptake by a low-iodine diet and thyroid-stimulating hormone (TSH) application. Efficacy of induction of hypothyroidism was tested by measurement of serum T₄ concentrations, pituitary TSHβ and liver deiodinase type 1 (DIO1) mRNA expression, body weight analysis, and ^99mTc-pertechnetate scintigraphy. While 200 µCi (7.4 MBq) ¹³¹I alone was not sufficient to abolish thyroidal T₄ production, 500 µCi (18.5 MBq) ¹³¹I combined with 1 week of a low-iodine diet decreased serum concentrations below the detection limit. However, the high ¹³¹I dose resulted in severe side effects. A combination of 1 week of a low-iodine diet followed by injection of bovine TSH before the application of 150 µCi (5.5 MBq) ¹³¹I decreased serum T₄ concentrations below the detection limit and significantly increased pituitary TSHβ concentrations. The systemic effects of induced hypothyroidism were shown by growth arrest and a decrease in liver DIO1 expression below the detection limit. ^99mTc-pertechnetate scintigraphy revealed absence of thyroidal ^99mTc-pertechnetate uptake in ablated mice. In summary, we report a revised protocol for radioiodide ablation of the thyroid gland in the mouse to generate an in vivo model that allows the study of thyroid hormone action using NIS as a reporter gene.

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“…Further on, it became evident that the lack of TSH preferentially decreased the number of pre-B lymphocytes in the mice bone marrow but, curiously, only the innate immune response was impaired [5]. Furthermore, depending on the model used, and severity of hypothyroidism, various results have been reported including a normal or decreased number of T cells and macrophages [3,6,7]. No study reported the increase in other cellular types.…”

Section: Introductionmentioning

confidence: 96%

“…The domestic animal species that is most commonly diagnosed to have hypothyroidism is the dog, but there is no data on what would be the effect of canine maternal hypothyroidism on their pups and specifi cally on their immunological status. Although the association between hypothyroidism and immunity is demonstrated [3,6,7], the importance of TH for the maturation of the spleen tissue compartments in the period of prenatal development, neonatal and juvenile periods have received little attention. A normally developed spleen should be the prerequist for normal clearance of circulating pathogens and thus the protection of animal from sepsis.…”

Section: Introductionmentioning

confidence: 99%

Stereological and Immunohistochemical Study of the Spleen in Hypothyroid Juvenile Rats

et al. 2015

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The purpose of this work was to investigate the infl uence of hypothyroidism on spleen tissue morphology and immune cell density in fourteen-day-old juvenile rats. Hypothyroidism in pups (n=10) was induced by administration of propylthiouracil (PTU) in drinking water (1.5 mg/L) to their mothers during pregnancy and period of lactation. Fourteen-day-old pups were sacrifi ced and the thyroid-stimulating hormone (TSH) serum concentration and thyroid activation index (Ia) were determined. Increased serum level of TSH and increased Ia showed that pups from PTU treated mothers were hypothyroid. White and red spleen pulp, marginal zone and connective tissue volume density has been assessed by using the stereological method. Using immunohistochemistry, the present CD3+ T lymphocytes, CD45RA+ B lymphocytes and CD68+ macrophages were quantifi ed. A signifi cant reduction of volume density of the periarteriolar lymphocyte sheath (Vv PALS ) and lymphatic follicles (Vvf) due to depletion of T and B lymphocytes respectively, was observed in the spleens of hypothyroid pups compared to controls. The volume density of the red pulp (Vvrp), marginal zone (Vvmz) and connective tissue (Vvct) was increased, as well as the number of CD68+ macrophages in the spleens of hypothyroid pups compared to controls. These results indicate that thyroid hormones might be important for normal development of both, specifi c and innate immune cells in the spleen during prenatal and early postnatal period.

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Methimazole-induced hypothyroidism causes cellular damage in the spleen, heart, liver, lung and kidney

Cited by 56 publications

References 24 publications

Acute Treatment with T-Type Calcium Channel Enhancer SAK3 Reduces Cognitive Impairments Caused by Methimazole-Induced Hypothyroidism Via Activation of Cholinergic Signaling

Acute Treatment with T-Type Calcium Channel Enhancer SAK3 Reduces Cognitive Impairments Caused by Methimazole-Induced Hypothyroidism Via Activation of Cholinergic Signaling

Establishment of an Effective Radioiodide Thyroid Ablation Protocol in Mice

Stereological and Immunohistochemical Study of the Spleen in Hypothyroid Juvenile Rats

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