Hyperthyroid Rats Research Articles

Assessment of the endocrine-disrupting effects of diethyl phosphate, a nonspecific metabolite of organophosphorus pesticides, by in vivo and in silico approaches

Organophosphorus pesticides (OPs) remain one of the most commonly used pesticides, and their detection rates and residues in agricultural products, foods and environmental samples have been underestimated. Humans and environmental organisms are at high risk of exposure to OPs. Most OPs can be degraded and metabolized into dialkyl phosphates (DAPs) in organisms and the environment, and can be present in urine as biomarkers for exposure to OPs, of which diethyl phosphate (DEP) is a high-exposure metabolite. Epidemiological and cohort studies have found that DAPs are associated with endocrine hormone disorders, especially sex hormone disorders and thyroid hormone disorders, but there has been no direct causal evidence to support these findings. Our study explored the effects of chronic exposure to DEP on endocrine hormones and related metabolic indicators in adult male rats at actual doses that can be reached in the human body. The results showed that chronic exposure to DEP could cause thyroid-related hormone disorders in the serum of rats, causing symptoms of hyperthyroidism in rats, and could also lead to abnormal expression of thyroid hormone-related genes in the rat liver. However, DEP exposure did not seem to affect serum sex hormone levels, spermatogenesis or sperm quality in rats. The molecular interactions between DEP and thyroid hormone-related enzymes/proteins were investigated by molecular docking and molecular dynamics methods in silico. It was found that DEP could strongly interact with thyroid hormone biosynthesis, blood transport, receptor binding and metabolism-related enzymes/proteins, interfering with the production and signal regulation of thyroid hormones. In vivo and in silico experiments showed that DEP might be a potential thyroid hormone-disrupting chemical, and therefore, we need to be more cautious and rigorous regarding organophosphorus chemical exposure.

Morphometric and Phasic Activity Changes of Urinary Bladder in Hyperthyroid Rats and the Possible Protective Effect of Folic Acid

Abstract Background: Hyperthyroidism was one of the most com-mon endocrine disorders. Urinary tract dysfunctions were common symptoms in hyperthyroid patients. Folic acid is affected by Thyroid dysfunction as hyperthyroidism is asso-ciated with subclinical deficiency and depletion of folate stores. Aim of Study: To study the morphometric and the in-vitro contractility changes of the urinary bladder in hyperthyroid rats, and the protective effect of folic acid and its possible mechanisms. Material and Methods: Forty male albino rats divided into four groups: Control, hyperthyroid, folic and (hyperthyroid + folic) groups. TSH, T3, T4, MDA & PGE2 were measured. Rats were then sacrificed. The weight, morphometric changes and phasic activity of the urinary bladder were assayed. Results: Hyperthyroid group significantly decreased TSH and increased T3 (Triiodothyronine), T4 (thyroxine), MDA (malondialdehyde) and PGE2 (prostaglandin E2), bladder weight, wall, and lumen areas with unchanged wall thickness, and increased smooth muscle and urothelium areas with unchanged collagen area and increase the contractile response of the urinary bladder strips to acetylcholine when compared to the control group. Co-administration of folic acid to hyper-thyroid rats significantly increased TSH and decreased T3, T4, MDA and PGE2, bladder weight, wall, lumen areas, smooth muscle, urothelium areas and the contractile response of the urinary bladder strips to acetylcholine when compared to the hyperthyroid group. Conclusions: Folic acid protects against enhanced bladder contractility and bladder remodeling in hyperthyroid rats possibly through ameliorating the increased thyroid hormones levels, anti-oxidative, and anti-inflammatory properties.

The role of fish oil in attenuating cardiac oxidative stress, inflammation and fibrosis in rat model of thyrotoxicosis

Hyperthyroidism is associated with cardiovascular complications. Fish oil reduces risk of cardiovascular diseases. This study aims to evaluate the impact of fish oil on myocardial oxidative stress, inflammation and fibrosis in rat model of thyrotoxicosis. Rats were randomized into four groups; control rats, fish oil treated rats (FO, 100mg omega-3/100g body weight/day), hyperthyroid rats (Hyper, i.p levothyroxine 3 mg/kg/day), and hyperthyroid rats treated with fish oil (Hyper + FO) for 8 weeks. Changes in oxidants/antioxidants, inflammatory and fibrotic markers were measured. Thyrotoxicosis increased serum endothelin-1, thiobarbituric acid reactive substances (TBARS) and reduced activities of cardiac catalase and super oxide dismutase (SOD). Cardiac fibrosis paralleled with a decrease of matrix metalloproteinase -2 (MMP2) levels were observed in Hyper group. Use of FO increased activities of SOD and catalase, increased TBARS levels, and attenuated cardiac fibrosis by normalizing MMP-2 levels. Use of FO may attenuate cardiac oxidative stress and fibrosis in hyperthyroid states.

P.772 Low frequency stimulus - induced long-term potentiation in aged hyperthyroid rats: possible roles of nitric oxide synthase

P.772 Low frequency stimulus - induced long-term potentiation in aged hyperthyroid rats: possible roles of nitric oxide synthase

The effect of eplerenone on the renin-angiotensin-aldosterone system of rats with thyroid dysfunction.

ObjectivesThis study was conducted to evaluate the effect of eplerenone on the RAAS and kidney function in rats with thyroid hormone disorders.MethodsThis study involved 30 male Wistar albino rats, divided into three groups. The first group (N = 6) served as a control. The second group involved 12 rats with experimentally induced hypothyroidism through receiving propylthiouracil (0.05% w/v) in drinking water for one month, which was divided into two subgroups of six rats each. The first subgroup served as a positive hypothyroid control, and the second subgroup received oral daily dose of eplerenone (100 mg/kg) for 14 days. The third group included 12 rats with induced hyperthyroidism with L‐thyroxin (0.0012% w/v) in drinking water, and rats in this group were also divided into two subgroups. The first subgroup served as a positive hyperthyroid control, and the second subgroup received oral eplerenone 100 mg/kg.ResultsEplerenone indicated a significant increase in renin and angiotensin I from 184.09 pg/ml and 178.66 pg/ml to 603.31 pg/ml and 250.88 pg/ml, respectively, meanwhile, aldosterone indicated no significant changes after inducing hypothyroidism and eplerenone administration.The induction of hyperthyroidism led to a significant increase in angiotensin I from 248.84 pg/ml to 292.22 pg/ml. Oral administration of eplerenone for 14 days caused a significant increase aldosterone from 364.23 pg/ml to 497.02 pg/ml.ConclusionEplerenone significantly increased the serum renin and angiotensin I in hypothyroid and aldosterone and angiotensin I in hyperthyroid rats. Aldosterone in hypothyroid rats was not changed by eplerenone.

Therapeutic Effect of Scutellaria baicalensis on L-Thyroxine-Induced Hyperthyroidism Rats.

Background This study was performed to evaluate the anti-hyperthyroidal effects and action mechanism of Scutellaria baicalensis Georgi (SB), a medicinal herb, on levothyroxine (LT4)-induced hyperthyroidal rats. Methods Male Wistar rats were divided into five groups, namely, euthyroidal normal group (Normal), hyperthyroidism control group (Control), hyperthyroidism plus PTU-treated group (PTU) as a positive control, hyperthyroidism plus 400 mg/kg SB-treated group (SB400), and hyperthyroidism plus 800 mg/kg SB-treated group (SB800). The rats in groups other than Normal were injected with LT4 for 2 weeks to induce hyperthyroidism and then were administrated each treatment for 2 weeks. Clinical symptoms and biomarkers related to hyperthyroidism were examined, and the gene expressions related to the regulation of thyroid hormone were determined. Results Compared with the Control group, pulse rate, serum T3, T4, triglyceride, thyroid follicle size, and the deiodinase 1 (Dio1) gene expression were significantly reduced in the SB and PTU groups. Serum TSH and the thyroxine-binding globulin (Tbg) gene expression were significantly increased in the SB and PTU groups. Conclusions These results suggest that SB might suppress T3, T4, and adrenergic activity by modulating Dio1 and Tbg expression, and therefore, SB could be an alternative therapy for hyperthyroidism.

"Evaluation of Anti Thyroid Activity of Asaparagus Racemosus Root Extract against Thyroxine Induced Hyperthyroidism in Rats"

"Evaluation of Anti Thyroid Activity of Asaparagus Racemosus Root Extract against Thyroxine Induced Hyperthyroidism in Rats"

Aliskiren, Fosinopril, and Their Outcome on Renin-Angiotensin-Aldosterone System (RAAS) in Rats with Thyroid Dysfunction.

Background and Objectives Thyroid hormones have an important role in the growth and development of various tissues including the kidney, which is the major site of renin release and the consequent angiotensin and aldosterone formation. Therefore any derangement in thyroid function can result in abnormal functioning in the renin-angiotensin-aldosterone system. The current study was undertaken to find the impact of using a direct renin inhibitor (Aliskiren) and an angiotensin-converting enzyme inhibitor (Fosinopril) on the components of the renin-angiotensin-aldosterone system (RAAS) in rats with thyroid dysfunctions. Method Forty-two male albino rats were divided into three subgroups. First group (6 rats) served as control. Second group (18 rats) served as hyperthyroid group (6 rats positive control, 6 rats given Aliskiren, and 6 rats given Fosinopril). Third group (18 rats) served as hypothyroid group (6 rats positive control, 6 rats given Aliskiren, and 6 rats given Fosinopril). Induction of hyperthyroidism and hypothyroidism was done through daily oral administration of L-Thyroxine and Propylthiouracil, respectively. On day 40 of the study, the rats were sacrificed and blood was collected for estimation of renin, angiotensin I, angiotensin II, aldosterone, TSH, T3, and T4. The collected blood samples were also used for estimation of levels blood urea, serum creatinine, liver enzymes, and serum electrolytes. Blood pressure and urine collection were done on days 1 and 40. The collected urine was used for estimation of urine flow, sodium excretion, and potassium excretion rates. Results In hypothyroid induced rats, serum renin level dropped as expected, while the use of Aliskiren and Fosinopril on these hypothyroid rats raised renin level due to the feedback mechanism. Both angiotensin I and II were significantly (P <0.05) lower than normal levels in the hypothyroid rats, unlike the level of aldosterone, which was higher than normal level. There was nonsignificant lowering in BP (systolic, diastolic, and mean BP) in the hypothyroid rats. Treatment of these rats with Aliskiren and Fosinopril did not lower the blood pressure more than normal when compared to the hypothyroid group. The hypothyroid rats also showed a decrease in level of serum creatinine. In hyperthyroid rats, there was a rise in levels of serum renin, angiotensin II, and aldosterone; nevertheless, the increase in angiotensin I level was significant. The use of Aliskiren and Fosinopril increased the level of renin nonsignificantly (decreased angiotensin I significantly). Hyperthyroid rats showed a significant increase in systolic, diastolic, and mean blood pressure. Both Aliskiren and Fosinopril increased urine flow, Na+ excretion, and K+ excretion rates. Aliskiren was better at reducing the high blood pressure. Conclusion Aliskiren and Fosinopril in hyperthyroid rats decreased serum angiotensin I, angiotensin II, and aldosterone. Blockade of renin and inhibition of angiotensin-converting enzyme both resulted in a rebound increase in level of renin in hypothyroid rats. Aliskiren is better at controlling blood pressure in hyperthyroid rats. Urine flow, sodium excretion, and potassium excretion rates were improved by the use of Aliskiren and Fosinopril in hyperthyroid rats.

Age-dependent evaluation of long-term depression responses in hyperthyroid rats: Possible roles of oxidative intracellular redox status

BackgroundAccording to the free radical theory, a gradual accumulation of the free radicals normally produced in the body underlies the changes associated with aging. Thyroid hormones (THs) are related to oxidative stress not only due to their stimulation of metabolism but also due to their effects on antioxidant mechanisms. Thyroid dysfunction increases with age; thus, changes in TH levels in elderly individuals could be a factor affecting the development of neurodegenerative diseases. However, the relationship is not always clear, based on current evidence regarding synaptic plasticity. MethodsHippocampal long-term depression (LTD) and oxidative status in the hippocampus were evaluated at two different ages (2–3 and 12–14 months) in male rats. Rats were administered 0.2 mg/kg/day of l-thyroxine for 21 days starting at postnatal day 40 to induce hyperthyroidism. LTD was induced in the dentate gyrus using low frequency stimulation of the perforant pathway. Spectrophotometry was performed to measure catalase (CAT), superoxide dismutase (SOD), and malondialdehyde (MDA) levels, glutathione peroxidase (GPx) activity, and total nitrite/nitrate (tNOx) and nitric oxide synthase (NOS) levels. ResultsA reliable LTD was elicited in young rats with hyperthyroidism, while the same protocol could induce a small magnitude of synaptic LTD in the absence of spike-LTD in control rats. In aged rats, controls did not express LTD, but a significant LTP of spike was induced in the absence of synaptic LTD in hyperthyroid rats. While CAT levels were significantly decreased, MDA levels were increased in the aged groups compared to the corresponding young groups. Young rats with euthyroidism had significantly lower GPx activity than each of the hyperthyroid groups. There was no significant difference in SOD levels among the groups. Compared with aged rats, young rats exhibited a hyperthyroidism-induced decrease in NOS levels. Nevertheless, neither the main effects of age and thyroxine administration nor the interaction between these factors reached significance for tNOx. ConclusionThese results indicate that hyperthyroidism-related changes in synaptic plasticity are modulated by aging. This modulation may explain the increased cognitive impairment in this disease at older ages, which probably depends on alterations in NOS levels.

Possible activation of NRF2 by Vitamin E/Curcumin against altered thyroid hormone induced oxidative stress via NF\u0138B/AKT/mTOR/KEAP1 signalling in rat heart

Oxidative stress is implicated in both hypo- and hyper-thyroid conditions. In the present study an attempt has been made to elucidate possible interaction between vitamin E or/and curcumin (two established antioxidants) with active portion (redox signaling intervening region) of nuclear factor erythroid 2-related factor 2 (NRF2) as a mechanism to alleviate oxidative stress in rat heart under altered thyroid states. Fifty Wistar strain rats were divided into two clusters (Cluster A: hypothyroidism; Cluster B: hyperthyroidism). The hypo- (0.05% (w/v) propylthiouracil in drinking water) and hyper- (0.0012% (w/v) T4 in drinking water) thyroid rats in both clusters were supplemented orally with antioxidants (vitamin E or/and curcumin) for 30 days. Interactive least count difference and principal component analyses indicated increase in lipid peroxidation, reduced glutathione level, alteration in the activities and protein expression of antioxidant enzymes like superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase under altered thyroid states. However, the expression of stress survival molecules; nuclear factor κB (NFκB) and the serine-threonine kinase B (Akt), in hyper-thyroidism only points towards different mechanisms responsible for either condition. Co-administration of vitamin E and curcumin showed better result in attenuating expression of mammalian target for rapamycin (mTOR), restoration of total protein content and biological activity of Ca2+ ATPase in hyperthyroid rats, whereas, their individual treatment showed partial restoration. Since NRF2 is responsible for activation of antioxidant response element and subsequent expression of antioxidant enzymes, possible interactions of both vitamin E or/and curcumin with the antioxidant enzymes, NRF2 and its regulator Kelch ECH associating protein (KEAP1) were studied in silico. For the first time, a modeled active portion of the zipped protein NRF2 indicated its interaction with both vitamin E and curcumin. Further, curcumin and vitamin E complex showed in silico interaction with KEAP1. Reduction of oxidative stress by curcumin and/or vitamin E may be due to modulation of NRF2 and KEAP1 function in rat heart under altered thyroid states.

Effect of Amindarone induced hyper thyriodism on bone remodeling process: histological and radiodensitometric analysis. (Experimental study in rats)

Objectives: The aim of the study was to evaluate the effect of Amindarone drug alone and in combination with cabbige on bone methabolism on both histological and radiographical .Subjects& Methods: 15 rats were allocated in three groups, in group (I) the rats received the amiodarone, group (II) rats received aminodarone and uncooked cabbage while group(III) serve as a control group, by the end of 13th week the rats were sacrified using an overdose of I.V. Phenobarbital.mandibles of the rats were subjected to histological and radiograghic examination .Results: on the radiographic examination of the rats’ mandible in group I that received the Amiodaron the bone density showed decrease with average of( 601 ± 203) while in group II that received the Amiodaron and cabbages showed less decrease in bone density with average of (730±160.4) than the control group (group III) that showed average of bone density of (830±139.5) there is a significant difference among the groups P<0.001.Conclusion: Amiodarone drug induced the hyperthyroidism in rats treated for 13 weeks. The use of un cooked cabbage decrease the changes in the bone in both histological and radiographic evaluations

Comparative Study of the Effects of Acute In Vitro and Short‐term In Vivo Treatments with 3, 5, 3′ Triiodo‐L‐Thyronine on Contractile Responsiveness of Isolated Rat Thoracic Aorta

This work was aimed to study comparatively the influences of acute in vitro and short‐term in vivo treatments with 3, 5, 3′ triiodo‐L‐thyronine (T3) on the contractile responsiveness of isolated rat thoracic aortas. Previous studies have reported that T3 through nongenomic and genomic mechanisms can elicit endothelium‐dependent and ‐independent, nitric oxide (NO)‐mediated, depression of vascular tone. Short‐term in vivo treatment (hyperthyroidism) was established by subcutaneous injections of T3 (500 mg/kg/day) for 3 days (T33d); while control rats received vehicle (alkaline saline solution) for 3 days (V3d). T33d treatment was sufficient to cause both significant weight loss and elevation of T3 serum levels in the rat. In endothelium‐intact aortic rings contracted with phenylephrine, in vitro application of increasing cumulative concentrations of T3, each 30 minutes (0.01, 0.1, 1 and 10 mM), did not alter the contractile tone compared to vehicle treated tissues. Likewise, in vitro treatment with T3 (0.1, 1 and 10 mM for 30 min or 2 hs) did not modify the relaxant responses induced by either acetylcholine or sodium nitroprusside, in that order, in endothelium‐intact and ‐denuded aortic rings contracted with phenylephrine. (In aortic rings with and without endothelium, phenylephrine‐induced precontractions were not modified by preceding exposure to T3 compared to their corresponding vehicle‐treated tissues.) The concentration‐dependent contractions caused by phenylephrine and angiotensin II in aortic rings with endothelium, remained unchanged in the presence of T3 (0.1, 1 and 10 mM) applied 30 min or 2 h before. On the other hand, T33d treatment significantly decreased the contractile responses induced by phenylephrine and angiotensin II in aortic rings with and without endothelium, related to their respective controls. The absence of endothelium or the addition of the NO synthase inhibitor, L‐NAME, in the presence of endothelium (100 mM), independently, enhanced the contractile responses to phenylephrine in aortic rings of T33d and V3d rats. However, the contractile responses to phenylephrine remained similarly depressed in endothelium‐denuded and endothelium‐intact L‐NAME‐treated aortas of T33d compared to V3d rats. In conclusion, T3 applied in vitro does not alter the development of active tone in the endothelium‐intact and ‐denuded thoracic aortas, which rules out a direct action, by a rapid non‐genomic mechanism, of this hormone in smooth muscle and endothelial cells. On the other hand, short‐term in vivo administration of T3 depressed contractile responsiveness of the thoracic aorta, independently of endothelium and NO (whether of endothelial or muscle origin). It remains to elucidate if the T3‐induced depression of aortic contractility is due to direct hormonal effects or is secondary to a hyperdynamic cardiovascular state in hyperthyroid rats.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Evaluation of Dennettia tripetala Baker F. Leaf Aqueous Extract Effect on Hyperthyroidism in Albino Rats

This study evaluated Dennettia tripetala leaf aqueous extract effect on hyperthyroidism in albino rats ( Rattus norvegicus ). It was conducted at the Department of Zoology and Environmental Biology, University of Nigeria, Nsukka. It lasted for seven weeks. Seventy-two male albino rats (Rattusnovergicus) weighing 66 – 108 g were assigned into six groups (A – F) with twelve rats (replicated three times, four rats per replicate) in each group. Three rats from each group were randomly selected and weighed before samples of blood were collected at days 7, 14, 21 and 28. Hyperthyroidism was induced in rats of groups B – F, orally with 600 µg/kg Levothyroxine for 14 days. Phytochemical screening of the extract was conducted. Whereas normal control (group A) and hyperthyroid control (group B) were fed water and food only, standard control (group C) received 1.35mg/kg of Carbimazole orally. The treatment groups were D – 100 mg/kg, E – 250 mg/kg and F – 500 mg/kg. Rats’body weights were determined at days 0, 7, 14, 21 and 28 during treatment. The extract’s effect on hyperthyroid induced rats total cholesterol (TC), triglyceride (TG), low-density lipoproteins (LDL), high-density lipoproteins (HDL), thyroid stimulating hormone (TSH), triiodothyronine (T3), tetraiodothyronine(T4) and histology of thyroid gland were evaluated. Phytochemical screening recorded some secondary metabolites. Toxicity (LD50) test recorded no lethal effect at the highest dose (5000 mg/kg) administered. The extract graded dose effect was most effective on body weight on Day 7. It also caused a significant increase (P<0.05) in TC, LDL-C, TG, and TSH but significantly decreased (P<0.05) HDL-C and T3 and T4 compared with hyperthyroid control. Micrographs from extract treated rats showed no histologic alteration. However, there were observed variations in body weight, LDL-C, TG, TSH and T 4 the body weight at day 0 due to age differences among animals used. Aqueous Dennettiatripetala leaf extract seems to possess potential for ameliorating post induced hyperthyroidism effects in rat. Keywords: Albino rat, Dennettia tripetala , Hyperthyroidism, Phytochemical screening, Lipid profile, Histopathology DOI : 10.7176/JNSR/9-8-05 Publication date : April 30 th 2019

Altered gene expression of hydrogen sulfide-producing enzymes in the liver and muscles tissues of hyperthyroid rats.

Thyroid hormones have a role in the regulation of hydrogen sulfide (H2 S) biosynthesis. In this study, we determined the effects of hyperthyroidism on H2 S levels in various tissues and messenger RNA (mRNA) expression of cystathionine-β-synthase (CBS), cystathionine-γ-lyase (CSE), and 3-mercaptopyruvate sulfurtransferase (3-MST) in the liver and muscles of the rat. Sixteen male Wistar rats were divided into the hyperthyroid and the control groups. Hyperthyroidism was induced by adding l-thyroxine (12 mg/L) to drinking water for a period of 21 days. H2 S concentrations in serum, liver, aorta, heart, and soleus muscles, as well as mRNA expressions of CBS, CSE, and 3-MST in these tissues were measured at Day 21. Hyperthyroid rats had lower H2 S levels in the serum compared with controls (14.7 ± 1.4 vs. 25.7 ± 1.6 µmol/L, p < 0.001). Compared with controls, hyperthyroid rats had lower levels of H2 S in the aorta (89%), heart (80%), and soleus (103%) muscles, but higher levels in the liver (35%). Hyperthyroidism decreased the ratio of CBS/CSE mRNA expression in the liver and the CSE/CBS mRNA expression in the muscles by decreasing CBS levels in liver (34% cf. controls) and CSE levels in the aorta, heart, and soleus muscles (respectively, 51%, 7%, and 52% cf.). In addition, hyperthyroidism decreased the mRNA expression of 3-MST in the liver (51%) and aorta (33%), and increased it in the heart (300%) and soleus muscle (182%). In conclusion, hyperthyroidism increased H2 S levels in the liver and decreased it in muscles; these effects are at least in part due to increases and decreases in expression of CSE in the liver and muscles, respectively. These data indicate an association between thyroid hormone status and gene expression of the H2 S-producing enzymes in the rat.

Effects of aqueous extract of polyherbal formulation against hyperthyroidism induced by L-thyroxin in a rat model

Background: Hyperthyroidism is a disorder that occurs when the thyroid gland secretes more thyroid hormone than the body needs. Thyroid hormone is essential for the normal growth and development of normal organs. Polyherb (POH) formulation has proven to be useful in number of diseases and has been used in folk medicine as an anti-hyperthyroidism, anti-oxidant, and appetitestimulating agent. The aim of the study was to evaluate the curative effect of POH against L-thyroxin (LT4)-induced hyperthyroidism in male rats.&#x0D; Methods: Seven groups (10 rats each) were used for this purpose. Determination of phytochemical analysis, oxidative stress markers, brain appetite marker and cell energy marker were determined via high-performance liquid chromatography (HPLC) techniques. Thyroid hormones were detected via ELISA, and liver functions were determined by colorimetric method.&#x0D; Results: The data showed that LT4 altered thyroid function via decreasing serum Thyroid-stimulating hormone (TSH), serum total protein, albumin and globulin, while increasing Triiodothyronine (T3), Thyroxine (T4), and Aspartate aminotransferase (AST). Moreover, oxidative stress markers in liver tissues were increased, via up-regulation of nitric oxide (NO), oxidized glutathione (GSSG), malondialdehyde (MDA), and 8-hydroxy-2'-deoxyguanosine (8OHdG). Meanwhile, glutathione (GSH) and ATP were alleviated; in contrast, metabolites of ADP and AMP were elevated. Neuronal appetite marker in brain tissue was decreased via low serotonin levels. On the other hand, rat groups treated with POH and Carbimazole (CBZ) showed markedly amelioration of hyperthyroidism in rats at low dose only but did not show complete amelioration at high dose of POH. The data were confirmed through histopathological examination of the thyroid.&#x0D; Conclusion: The data obtained demonstrated that POH, at low dose, can be very effective for completely treating hyperthyroidism in rats, and was safer than Carbimazole (CBZ) and ameliorated most signaling pathways and in different tissues.

Thyroid Disorders Change the Pattern of Response of Angiotensinase Activities in the Hypothalamus-Pituitary-Adrenal Axis of Male Rats.

Thyroid disorders affect the hypothalamic-pituitary-adrenal axis with important consequences on the cardiovascular function in which the renin-angiotensin system plays a major role. Hypo and hyperthyroidism influence the classic main components of the renin-angiotensin system. However, the behavior of other elements of the renin-angiotensin system such as Ang III, Ang 2-10, Ang IV, or AT4, regulated by angiotensinase enzymes such as alanyl- (AlaAP), cystinyl- (CysAP), glutamyl- (GluAP), or aspartyl-aminopeptidase (AspAP), has not yet been described. In order to obtain a comprehensive view on the response of the renin-angiotensin system in the hypothalamic-pituitary-adrenal axis of animals with thyroid disorders, these enzyme activities were simultaneously analyzed fluorometrically, using arylamide derivatives as substrates in hypothalamus, anterior and posterior pituitary, adrenals and plasma of euthyroid, hypothyroid, and hyperthyroid rats, and their intra- and inter-tissue correlations were evaluated. The response is depending on the type of enzyme studied, its location and the thyroid status. Anterior pituitary, adrenals and plasma were mainly affected by the thyroid disorders. In the anterior pituitary, GluAP and AspAP increased in hypothyroid rats. In adrenals, AlaAP and CysAP decreased in hypothyroid whereas GluAP and AspAP decreased in hyperthyroid rats. In plasma, while AlaAP increased in hypo- and hyperthyroid rats, CysAP and GluAP decreased only in hyperthyroid. In comparison with euthyroid, intra-tissue correlations decreased in hypothyroid but inter-tissue correlations decreased mainly in hyperthyroid rats. Thyroid disorders also produced a disruption in the pattern of inter-tissue correlations observed in euthyroid. These results suggest that thyroid hormone levels hit components of the renin-angiotensin system and may influence the paracrine and endocrine cross talk between cells.

Design, Synthesis, Molecular Modeling, and Biological Evaluation of Novel Thiouracil Derivatives as Potential Antithyroid Agents.

Hyperthyroidism is the result of uncontrolled overproduction of the thyroid hormones. One of the mostly used antithyroid agents is 6-n-propyl-2-thiouracil (PTU). The previously solved X-ray crystal structure of the PTU bound to mammalian lactoperoxidase (LPO) reveals that the LPO-PTU binding site is basically a hydrophobic channel. There are two hydrophobic side chains directed towards the oxygen atom in the C-4 position of the thiouracil ring. In the current study, the structural activity relationship (SAR) was performed on the thiouracil nucleus of PTU to target these hydrophobic side chains and gain more favorable interactions and, in return, more antithyroid activity. Most of the designed compounds show superiority over PTU in reducing the mean serum T4 levels of hyperthyroid rats by 3% to 60%. In addition, the effect of these compounds on the levels of serum T3 was found to be comparable to the effect of PTU treatment. The designed compounds in this study showed a promising activity profile in reducing levels of thyroid hormones and follow up experiments will be needed to confirm the use of the designed compounds as new potential antithyroid agents.

Size dependent effects of Gold Nanoparticles in ISO-induced Hyperthyroid Rats

In this study, we applied different sizes of gold nanoparticles (Au-NPs) to isoproterenol (ISO)-induced hyperthyroid heart disease rats (HHD rats). Single dose of 5, 40, 100 nm Au-NPs were injected intravenously. Cardiac safety tests were evaluated by cardiac marker enzymes in serum and cardiac accumulation of Au-NPs were measured by ICP-MS. Our results showed that size-dependent cardiac effects of Au-NPs in ISO-induced hyperthyroid rats. 5 nm Au-NPs had some cardiac protective effect but little accumulation in heart, probably due to smaller size Au-NPs can adapt to whole body easily in vivo. Histological analysis and TUNEL staining showed that Au-NPs can induce pathological alterations including cardiac fibrosis, apoptosis in control groups, however they can protect HHD groups from these harmful effects. Furthermore, transmission electron microscopy and western blotting employed on H9C2 cells showed that autophagy presented in Au-NPs treated cells and that Au-NPs can decrease LC3 II turning to LC3 I and decrease APG7 and caspase 12 in the process in HHD groups, while opposite effects on control groups were presented, which could be an adaptive inflammation reacts. As there are few animal studies about using nanoparticles in the treatment of heart disease, our in vivo and in vitro studies would provide valuable information before they can be considered for clinical use in general.

Effects of the Pharmacopuncture with MOK on Immune Regulation by Th1/Th2 Cytokines in L-Thyroxine-Induced Hyperthyroid Rats

Effects of the Pharmacopuncture with MOK on Immune Regulation by Th1/Th2 Cytokines in L-Thyroxine-Induced Hyperthyroid Rats

Therapeutic effects of acupuncture with MOK, a polyherbal medicine, on PTU-induced hypothyroidism in rats.

Acupuncture with MOK, a polyherbal medicine (MOK pharmacopuncture), has been used for the treatment of thyroid syndromes including hypothyroidism and hyperthyroidism in traditional Korean medicine. The present study investigated the effect of MOK pharmacopuncture on hypothyroidism and the mechanism underlying its antioxidation and immune regulation effects. Hypothyroidism was induced in Sprague-Dawley rats by subcutaneous injection of Propylthiouracil (PTU; 10 mg/kg) once daily for 4 weeks. MOK was administered by acupuncture on the acupoints around the thyroid gland of PTU-induced hypothyroidism rats once daily for 2 weeks following hypothyroidism induction. Administration of MOK pharmacopuncture significantly increased the PTU-induced decrease in body temperature of hypothyroidism rats. The weights of the spleen were also significantly decreased in hyperthyroidism rats following MOK pharmacopuncture. MOK pharmacopuncture significantly decreased the thyroid stimulating hormone level and increased the T3 and T4 levels in hypothyroidism rats. Administration of MOK pharmacopuncture significantly increased the glucose levels and decreased the levels of triglycerides, total cholesterol, low-density lipoprotein-cholesterol, and alanine transaminase in the sera of hypothyroidism rats. The expression of transient receptor potential cation channel subfamily V member 1 was increased in dorsal root ganglion and brain tissues by administration of MOK pharmacopuncture, and glutathione levels and the expression of superoxide dismutase 1 and catalase were increased in the liver and brain tissues. Administration of MOK pharmacopuncture significantly inhibited interferon-γ expression and increased the expression of interleukin (IL)-4, IL-10, and Forkhead Box P3 in the spleen tissues of hypothyroidism rats. In histological analysis, the administration of MOK pharmacopuncture improved the pathological features in the thyroid glands of hypothyroidism rats. The results suggested that the administration of pharmacopuncture may ameliorate the pathological progression of hypothyroidism by multiple actions, including normalization of the hypothyroidism-induced thyroid hormone imbalance, stimulation of the antioxidant defense system, and regulation of the T helper (Th)1/Th2 imbalance. Therefore, MOK extract may be used for the treatment of hypothyroidism in Korean clinics as a useful pharmacopuncture medicine.