Hyperthyroid Rats Research Articles

Effects of thyroid hormones on the antioxidative status in the uterus of young adult rats.

Thyroid hormones and oxidative stress play significant roles in the normal functioning of the female reproductive system. Nitric oxide (NO), a free radical synthesized by nitric oxide synthases (NOS), participates in the regulation of thyroid function and is also a good biomarker for assessment of the oxidative stress status. Therefore, the purpose of this study was to investigate effects of thyroid hormones on uterine antioxidative status in young adult rats. Thirty immature female Sprague-Dawley rats were randomly divided into three groups: control, hypothyroid (hypo-T) and hyperthyroid (hyper-T). The results showed the body weights decreased significantly in both the hypo-T and hyper-T groups and that uterine weights were decreased significantly in the hypo-T group. The serum concentrations of total triiodothyronine (T3) and thyroxine (T4), as well as estradiol (E2), were significantly decreased in the hypo-T group, but increased in the hyper-T group. The progesterone (P4) concentrations in the hypo- and hyperthyroid rats markedly decreased. Immunohistochemistry results provided evidence that thyroid hormone nuclear receptor α/β (TRα/β) and three NOS isoforms were located in different cell types of rat uteri. The NO content and total NOS and inducible NOS (iNOS) activities were markedly diminished in the hypo-T group but increased in the hyper-T group. Moreover, the activities of both glutathione peroxidase (GSH-Px) and catalase (CAT) exhibited significant decreases and increases in the hypo-T and hyper-T groups, respectively. The malondialdehyde (MDA) contents in both the hypo-T and hyper-T groups showed a significant increase. Total superoxide dismutase (T-SOD) activity in the hypo- and hyper-T rats markedly decreased. In conclusion, these results indicated that thyroid hormones have an important influence on the modulation of uterine antioxidative status.

The study of metabonomics combined with diversity of intestinal flora in LDP intervention in kidney-yin deficiency hyperthyroid rats

This study was to clarify the drug mechanism in the preparation of high-content plant polysaccharides.

Oestrogen Receptor Alpha and Progesterone Receptor in Uterus and Ovaries on Different Days of The Oestrus Cycle in Hyperthyroid Rats

Background: The present study evaluated, in different oestrus cycle phases, the oestrogen receptor alpha (ERα) and progesterone receptor (PgR) in rates with hyperthyroid ovaries and uterus.Materials and Methods: Sixty-four adult female wistar albino rats were used. Animals were randomly separated into eight different groups, four of which constituted the control group and the other four of which were the actual experimental group. Hyperthyroidism was induced by daily s.c. injection of L-thyroxine (L-T4, 250 µg/kg) for 21 days.Results: Hyperthyroidism induced decreased plasma TSH levels and increased plasma free T4 levels (P < 0.001). In addition, it increased plasma oestrogen levels in all cycle phases, and plasma progesterone levels increased in different cycle phases, excluding the oestrus phase, in rats (P < 0.01). By the end of the experiment, ERα percentages were decreased in oestrus days in uterine luminal epithelium; however, ERα percentages were increased in metoestrus phases in hyperthyroid rats. ERα was elevated in proestrus, metoestrus and dioestrus phases in the corpus luteum, and hyperthyroidism also increased ERα percentages in theca folliculi. In uterine luminal epithelium, the hyperthyroidism group showed higher expressions of PgR (P < 0.05) in oestrus and metoestrus phases and decreased oestrus phase compared to control rats.Conclusions: As a result, we conclude that both the levels of plasma estrogen and progesterone as well as the differences in the distributions of relevant receptors in ovarian and uterus tissues have an impact on female infertility due to hyperthyroidism. DOI: http://dx.doi.org/10.3126/ajms.v6i4.11816 Asian Journal of Medical Sciences Vol.6(4) 2015 14-20

EFFECT OF CARROT OIL SUPPLEMENTATION ON OXIDATIVE STRESS IN EXPERIMENTALLY-INDUCED HYPOTHYROIDISM AND HYPERTHYROIDISM IN ALBINO RATS

It is estimated that huge amount of ROS, especially of H2O2, are produced in the thyroid under physiological conditions, justifying the statement that the thyroid gland is an organ of “oxidative nature”. The present study is designed to evaluate the effect of carrot oil administration on hormonal & lipid profile, lipid peroxidation and antioxidant & minerals status in both hypothyroid and hyperthyroid male albino rats. Rats were rendered hyperthyroid by exogenous thyroxine (0.3 mg/kg body weight) and hypothyroid by carbimazole (20 mg/kg body weight). Then, these rats were orally administered carrot oil (100 mg/kg body weight) for 4 weeks. Thyroid stimulating hormone (TSH) showed its highest level with the hypothyroid group and its lowest level with the hyperthyroid group. Triiodothyonine (T3) and thyroxine (T4) levels were increased significantly in hyperthyroid group and deceased significantly in hypothyroid one in comparison with the control group. Both non enzymatic (reduced glutathione, GSH; vitamins E and C) and enzymatic (catalase, CAT; glutathione peroxidase, GSHPx; glutathione reductase, GSSGR; and glucose-6-phosphate dehydrogenase, G6PDH) antioxidant defenses were decreased in hepatic tissues of both hypothyroid and hyperthyroid rats. On the other hand, lipid peroxidation products increased significantly in these considered groups. The highest levels of triglyceride, total cholesterol, and bad lipoproteins (LDL- and vLDL-cholesterol) were recorded in hypothyroid group, whereas they showed lowest level in hyperthyroid one. Opposite change was observed in HDL-cholesterol level, where it achieved its highest level in hyperthyroid group and its lowest level in hypothyroid rats. Moreover, apolipoproteins (A and B) increased significantly in the hyperthyroid group and decreased in the hypothyroid group. In hyperthyroid rats, the serum levels of calcium, magnesium and zinc increased significantly and phosphorus level decreased significantly as compared to the control group. Reverse results were obtained in hypothyroid rats. Carrot oil administration improved the above mentioned alterations. These effects of carrot oil may help the improvement of hypo- and hyperthyroidisms and accompanied hepatic antioxidants defense system, but active compound searches should be proceeding in future.

Cardioprotective properties of citicoline against hyperthyroidism-induced reperfusion damage in rat hearts.

Hyperthyroidism represents an increased risk factor for cardiovascular morbidity, especially when the heart is subjected to an ischemia/reperfusion process. The aim of this study was to explore the possible protective effect of the nucleotide citicoline on the susceptibility of hyperthyroid rat hearts to undergo reperfusion-induced damage, which is associated with mitochondrial dysfunction. Hence, we analyzed the protective effect of citicoline on the electrical behavior and on the mitochondrial function in rat hearts. Hyperthyroidism was established after a daily i.p. injection of triiodothyronine (at 2 mg/kg of body weight) during 5 days. Thereafter, citicoline was administered i.p. (at 125 mg/kg of body weight) for 5 days. In hyperthyroid rat hearts, citicoline protected against reperfusion-induced ventricular arrhythmias. Moreover, citicoline maintained the accumulation of mitochondrial Ca(2+), allowing mitochondria to reach a high transmembrane electric gradient that protected against the release of cytochrome c. It also preserved the activity of the enzyme aconitase that inhibited the release of cytokines. The protection also included the inhibition of oxidative stress-induced mDNA disruption. We conclude that citicoline protects against the reperfusion damage that is found in the hyperthyroid myocardium. This effect might be due to its inhibitory action on the permeability transition in mitochondria.

Effect of Melatoninergic Drugs on the Specific Activity of Glutathione Redox-Cycle Enzymes in Experimental Hyperthyroidism

The effect of melatoninergic drugs [melaxen and agomelatine (Valdoxan)] on the activity of glutathione antioxidant system enzymes and NADPH suppliers was investigated for experimental hyperthyroidism in rats. The administration of these protectors at the pathology was accompanied by a change of the specific activity of glutathione reductase (EC 1.6.4.2), glutathione peroxidase (GP, EC 1.11.1.9), glutathione transferase (GT, EC 2.5.1.18), NADP-isocitrate dehydrogenase (NADP-IDH, EC 1.1.1.41), and glucose-6-phosphate dehydrogenase (G6PDH, EC 1.1.1.49) in rat liver, heart, and blood serum toward the control values. Apparently, this effect was related to a decreased load on the glutathione antioxidant system due to effective interaction of melatonin with free radicals upon correction of its level by melaxen and agomelatine.

Thermogenesis and longevity in mammals. Thyroxin model of accelerated aging

Development of experimental models of life span regulation is an important goal of modern gerontology. We proposed a thyroxin model of accelerated aging. Male Wistar rats at the age of 17months received thyroxin in drinking water at a concentration of 6mg/L for 2months as a model of induced hyperthyroidism (IH). Administration of thyroxin resulted in a decrease in life span and a 2°C increase in body temperature that was accompanied by a 2 fold increase in thyroxin level and a 40% increase in triiodothyronine in blood serum. Induced hyperthyroidism can be used as a model of accelerated aging. We also found that thyroxin administration acts as uncoupler of oxidative phosphorylation as treatment was accompanied by an increase in the generation of superoxide radicals by 50%. Antioxidant enzyme activity remained unchanged (glutathione peroxidase, glutathione reductase mitochondrial) or was reduced (glutathione-S-transferase by 1.7 times) as compared with the control. The activity of glucose-6-transferase was increased by 2.8 times as compared with control, and malate dehydrogenase activity in liver increased by 6.8 times. Induced hyperthyroidism in rats resulted in distinct epigenotype which was accompanied by a decrease in life span.

Experimentally induced hyperthyroidism influences oxidant and antioxidant status and impairs male gonadal functions in adult rats.

The objective of the present experiment was to study the effect of hyperthyroidism on male gonadal functions and oxidant/antioxidant biomarkers in testis of adult rats. Induction of hyperthyroidism by L-thyroxine (L-T4, 300 μg kg(-1) body weight) treatment once daily for 3 or 8 weeks caused a decrease in body weight gain as well as in absolute genital sex organs weight. The epididymal sperm counts and their motility were significantly decreased in a time-dependent manner following L-T4 treatment. Significant decline in serum levels of luteinising hormone, follicle stimulating hormone and testosterone along with significant increase in serum estradiol level was observed in hyperthyroid rats compared with euthyroid ones. Significant increase in malondialdehyde and nitric oxide concentration associated with significant decrease in superoxide dismutase and catalase activity was also noticed following hyperthyroidism induction. Both reduced glutathione content and glutathione peroxidase activity were increased in hyperthyroid rats compared with control rats. Marked histopathological alterations were observed in testicular section of hyperthyroid rats. These results provide evidence that hypermetabolic state induced by excess level of thyroid hormones may be a causative factor for the impairment of testicular physiology as a consequence of oxidative stress.

Antithyroid effects of naringin, hesperidin and rutin in l-T4 induced hyperthyroid rats: Possible mediation through 5′DI activity

BackgroundInvestigations are meager on the ameliorative role of plant based active compounds in regulating hyperthyroidism. We have now explored the possible role of three flavonoids in the regulation of L-thyroxine (l-T4)-induced hyperthyroidism in rats. This investigation attempts to reveal whether rutin, naringin and hesperidin supplementation exhibit antithyroid effects in L-T4-induced hyperthyroid rats and to work out the possible involvement of free radicals in their mode of action. MethodsEither rutin or naringin or hesperidin (50mg/kg each) was administered to L-T4-induced hyperthyroid rats for two weeks and their effects were evaluated on the alterations in levels of thyroid hormones, 5′-deiodinase I (5′DI) activity, hepatic lipid peroxidation as well as in antioxidants. Resultsl-T4 administration significantly enhanced the serum concentrations of thyroxine and triiodothyronine; the activities of hepatic 5′DI, serum lactate dehydrogenase and serum glutamate pyruvate transaminase along with an increase in content of malondialdehyde in hepatic tissues, but depleted the cellular antioxidants. However, on administration of the test flavonoids, these effects were more or less normalized. Electro paramagnetic resonance (EPR) spectra also indicated the suppression of the hydroxyl radicals (OH) in the hepatic tissues. ConclusionRutin, naringin and hesperidin have the potential to inhibit thyroid functions without hepatotoxicity and the effects are possibly mediated through their free radical scavenging action as evidenced by EPR study. From the comparative analyses of the results, rutin appeared to be the most effective one suggesting its better antithyroid and antioxidative potential over other two.

Dietary salt restriction in hyperthyroid rats. Differential influence on left and right ventricular mass.

This study assessed the impact of salt restriction on cardiac morphology and biochemistry and its effects on hemodynamic and renal variables in experimental hyperthyroidism. Four groups of male Wistar rats were used: control, hyperthyroid, and the same groups under low salt intake. Body weight, blood pressure (BP), and heart rate (HR) were recorded weekly for 4 weeks. Morphologic, metabolic, plasma, cardiac, and renal variables were also measured. Low salt intake decreased BP in T(4)-treated rats but not in controls. Low salt intake reduced relative left ventricular mass but increased absolute right ventricular weight and right ventricular weight/BW ratio in both control and hyperthyroid groups. Low salt intake increased Na(+)/H(+) exchanger-1 (NHE-1) protein abundance in both ventricles in normal rats but not in hyperthyroid rats, independently of its effect on ventricular mass. Mammalian target of rapamycin (mTOR) protein abundance was not related to left or right ventricular mass in hyperthyroid or controls rats under normal or low salt conditions. Proteinuria was increased in hyperthyroid rats and attenuated by low salt intake. In this study, low salt intake produced an increase in right ventricular mass in normal and hyperthyroid rats. Changes in the left or right ventricular mass of control and hyperthyroid rats under low salt intake were not explained by the NHE-1 or mTOR protein abundance values observed. In hyperthyroid rats, low salt intake also slightly reduced BP and decreased HR, proteinuria, and water and sodium balances.

Slow to fast muscle transformation following heterochronous isotransplantation is influenced by host thyroid hormone status.

We studied the effect of regeneration, altered innervation and thyroid hormone (TH) levels on fiber type transitions in slow soleus (SOL) muscles grafted (GRAFT) into host extensor digitorum longus (EDLh) muscles of euthyroid (EU), hyperthyroid (HT) and hypothyroid (HY) Lewis strain rats. SOL muscles were excised from 3-week to 4-week-old inbred Lewis rats and intramuscularly transplanted into EDLh muscles of 2-month-old female rats of the same strain. The proportions of type 1, 2A, 2X and 2B fibers of GRAFT were determined by immunohistochemistry and compared with those of EDLh muscle and EDL and SOL muscles of the unoperated contralateral hind limb. After an average regeneration period of 6-7 months and after being reinnervated by the "fast" peroneal nerve of EDLh muscle, GRAFT was transformed into a fast muscle. However, the extent of GRAFT transformation varied with different TH states. In the EU rats, GRAFT contained about 95 % of fast fibers, among which type 2X and 2B fibers predominated (about 75 %). The transition toward fast muscle phenotype was more pronounced in HT status, where the fastest type 2B fibers predominated. On the contrary, in HY status, the slow to fast transformation was less pronounced, as GRAFT contained less type 2B and 2X but more type 2A and 1 fibers. We conclude that the type of innervation is the crucial factor for the slow to fast fiber type transitions in GRAFT, but the extent of muscle transformation is further modulated by altered TH status.

Antiarrhythmic effect of tamoxifen on the vulnerability induced by hyperthyroidism to heart ischemia/reperfusion damage

Hyperthyroidism, known to have deleterious effects on heart function, and is associated with an enhanced metabolic state, implying an increased production of reactive oxygen species. Tamoxifen is a selective antagonist of estrogen receptors. These receptors make the hyperthyroid heart more susceptible to ischemia/reperfusion. Tamoxifen is also well-known as an antioxidant. The aim of the present study was to explore the possible protective effect of tamoxifen on heart function in hyperthyroid rats. Rats were injected daily with 3,5,3′-triiodothyronine at 2mg/kg body weight during 5 days to induce hyperthyroidism. One group was treated with 10mg/kg tamoxifen and another was not. The protective effect of the drug on heart rhythm was analyzed after 5min of coronary occlusion followed by 5min reperfusion. In hyperthyroid rats not treated with tamoxifen, ECG tracings showed post-reperfusion arrhythmias, and heart mitochondria isolated from the ventricular free wall lost the ability to accumulate and retain matrix Ca2+ and to form a high electric gradient. Both of these adverse effects were avoided with tamoxifen treatment. Hyperthyroidism-induced oxidative stress caused inhibition of cis-aconitase and disruption of mitochondrial DNA, effects which were also avoided by tamoxifen treatment. The current results support the idea that tamoxifen inhibits the hypersensitivity of hyperthyroid rat myocardium to reperfusion damage, probably because its antioxidant activity inhibits the mitochondrial permeability transition.

Cardiac microvascular rarefaction in hyperthyroid rats is reversed by losartan, diltiazem, and propranolol

Cardiac microvascular rarefaction appears to be involved in hyperthyroidism-induced left ventricular hypertrophy and dysfunction. We investigated the effects of losartan, an AT1 receptor antagonist; diltiazem, a calcium channel blocker; and propranolol, a β-adrenergic receptor antagonist, on cardiac function and structural microcirculatory cardiac alterations in an experimental model of l-thyroxin-induced hyperthyroidism in rats. Hyperthyroidism (HYPER) was induced by intraperitoneal injections of l-thyroxin for 35days (600μg/kg/day; n=32). The euthyroid group was treated with distilled water (EUT+VEH; n=8). On the 14th day, the HYPER group was divided into four groups that received an oral treatment for 21 days with saline (HYPER+VEH; n=8), losartan (10mg/kg/day; HYPER+LOS, n=8), diltiazem (10mg/kg/day; HYPER+DILT, n=8), or propranolol (10mg/kg/day; HYPER+PROP, n=8). An echocardiographic study was performed at baseline, at the beginning and at the end of the pharmacological treatment protocol (35th day). The structural capillary density in the left ventricle (LV) was analyzed using histochemical analysis with fluorescein isothiocyanate-conjugated Griffonia simplicifolia lectin. HYPER+VEH (182±5mmHg; P<0.001) presented higher systolic blood pressure (SBP) compared with EUT+VEH (132±3mmHg). HYPER+LOS (144±2mmHg), HYPER+DILT (147±3mmHg) and HYPER+PROP (153±4mmHg) presented lower SBP compared with HYPER+VEH (P<0.001). Chronic treatment with losartan, diltiazem, and propranolol reversed cardiac structural microvascular rarefaction (HYPER+VEH 0.16±0.01; EUT+VEH 0.35±0.02; HYPER+LOS 0.46±0.03; HYPER+DILT 0.49±0.02; HYPER+PROP 0.58±0.04 (Vv[cap]/Vv[fib]); P<0.001) and enhanced the LV ejection fraction of hyperthyroid rats (HYPER+VEH 71±3; EUT+VEH 85±2; HYPER+LOS 90±3; HYPER+DILT 85±3; HYPER+PROP 86±2%; P<0.05). In conclusion, chronic treatment with losartan, diltiazem, and propranolol improved the cardiac microcirculation and function in an experimental model of hyperthyroidism in rats.

Thyroxine-induced cardiac hypertrophy: Role of ascorbic acid in treatment

The heart is a major target organ for thyroid hormone action and marked changes occur in cardiac function in the case of hypo- or hyperthyroidism. Hyperthyroidism is a common metabolic disorder with prominent cardiovascular manifestation. We studied the changes in the heart structure and functions of hyperthyroid rat and ameliorating and protective role of ascorbic acid in treatment. Fourty male albino rats were equally divided into five groups; the first and second groups were the control and ascorbic acid groups respectively. Third group was the hyperthyroid rat group while 4th and 5th groups were co- and post-treated hyperthyroid rat with ascorbic acid respectively. Serum T3 and T4 levels were significantly increased also; TSH levels were significantly decreased in hyperthyroid rat as compared to control rat groups. Cholesterol, triglyceride, LDL-c and VLDL-c were significantly decreased when compared with control group. Many of abnormalities as severe hydrophobic changes of myofibrillar structure with striations, hypertrophy, cytoplasmic vacuoles and marked increase in desmin immunoreactivity were observed in left ventricle in hyperthyroid rats. Treatment with ascorbic acid helps in improving the adverse effect of hypothyroidism and also the histopathological and desmin immunoreactivity results confirms this finding.

Participation of Nitric Oxide in the Salivary Secretion of Hyperthyroid Rats

Participation of Nitric Oxide in the Salivary Secretion of Hyperthyroid Rats

Participation of Prostaglandin in the Salivary Secretion of Hyperthyroid Rats

The salivary glands have a high rate of metabolism and blood flow and indirectly depend on thyroid function. In the present study the influence of prostaglandin (PG) on salivary secretion in hyperthyroid rats was investigated. Study Design: Male Wistar rats, initial weight of 220 g, were distributed into two groups, euthyroid (EU) or hyperthyroid (HYPER), and treated with thyroxine (300μg/Kg; s.c; 7 days). EU and HYPER rats received meloxicam (MLX; 0.5 mg/kg; i.p.), a preferential cyclooxygenase-2 (COX-2) inhibitor, 30 minutes before salivary stimulation with pilocarpine (5 mg/kg; i.p.). Saliva was collected over a 15-minute period (μL/min/100 g body wt.) from the time of the first drop of saliva. Results: Hyperthyroidism increased salivary flow rate. COX-2 did not alter salivary flow in either group of rats (Mann-Whitney test; p < 0.05). Conclusion: COX-2 inhibition and, consequently, the synthesis of PGs by the injection of MLX, a non-steroidal anti-inflammatory drug, did not modulate the salivary secretion of HYPER rats.

The Effects of Ischemic Postconditioning on Myocardial Function and Nitric Oxide Metabolites Following Ischemia-Reperfusion in Hyperthyroid Rats

Ischemic postconditioning (IPost) could decrease ischemia-reperfusion (IR) injury. It has not yet reported whether IPost is useful when ischemic heart disease is accompanied with co-morbidities like hyperthyroidism. The aim of this study was to examine the effect of IPost on myocardial IR injury in hyperthyroid male rats. Hyperthyroidism was induced with administration of thyroxine in drinking water (12 mg/L) over a period of 21 days. After thoracotomy, the hearts of control and hyperthyroid rats were perfused in the Langendorff apparatus and subjected to 30 minutes global ischemia, followed by 120 minutes reperfusion; IPost, intermittent early reperfusion, was induced instantly following ischemia. In control rats, IPost significantly improved the left ventricular developed pressure (LVDP) and ±dp/dt during reperfusion (p<0.05); however it had no effect in hyperthyroid rats. In addition, hyperthyroidism significantly increased basal NOx (nitrate+nitrite) content in serum (125.5±5.4 µmol/L vs. 102.8±3.7 µmol/L; p< 0.05) and heart (34.9±4.1 µmol/L vs. 19.9±1.94 µmol/L; p<0.05). In hyperthyroid groups, heart NOx concentration significantly increased after IR and IPost, whereas in the control groups, heart NOx were significantly higher after IR and lower after IPost (p< 0.05). IPost reduced infarct size (p<0.05) only in control groups. In hyperthyroid group subjected to IPost, aminoguanidine, an inducible nitric oxide (NO) inhibitor, significantly reduced both the infarct size and heart NOx concentrations. In conclusion, unlike normal rats, IPost cycles following reperfusion does not provide cardioprotection against IR injury in hyperthyroid rats; an effect that may be due to NO overproduction because it is restored by iNOS inhibition.

Role of angiotensin Ⅱ type 1 receptor agonistic autoantibody in cardiac hypertrophy of hyperthyroidism rats and its relationship with PI3K/Akt signaling pathway

Objective To investigate the serum level of angiotensin Ⅱ type 1receptor(AT1R)agonistic autoantibody(AT1-AA)in hyperthyroidism rats with cardiac hypertrophy and the expression of PI3Kand protein kinase B(Akt)in cardiac tissue,so as to study the relationship between AT1-AA and PI3K/Akt signaling pathway.Methods Hyperthyroidism rats models were established by gavaging with levothyroxine sodium.Totally 54 SD rats were divided into three groups: hyperthyroidism group(group A),hyperthyroidism+olmesartan group(group B)and control group(group C).The heart weight index(HWI)and atrial natriuretic peptide(ANP)mRNA were taken as the indices for cardiac hypertrophy.Serum AT1-AA level was determined by enzyme-linked immunosorbent assay(ELISA),and the expression of AT1R and PI3K/ Akt was detected by Western blotting analysis.According to the determination results of AT1-AA,group A and B rats weresubdivided into AT1-AA positive group and negative group;the expressions of AT1R and PI3K/Akt were compared between these groups.Results(1)Compared with group C,HWI and the expression of ANP mRNA in group A and B were significantly increased(all P0.05);and those in group A were significantly higher than those in group B(P0.05).(2) The positive rates and ODvalues of AT1-AA in group A and B(61.11%,72.22% and 0.44±0.12,0.49±0.08)were significantly higher than those in group C(16.67%and 0.28±0.05)(all P0.01).(3)The expressions of AT1R and PI3K/p-Akt in group A and B were significantly higher than those in group C(P0.05,P0.01).Compared with group A,the expression levels of PI3K,p-Akt were significantly decreased in group B(P0.01,P0.05).(4)In group A,the expression levels of PI3Kand p-Akt in AT1-AA positive group were significantly higher than those in AT1-AA negative group(P0.01);in group B,the expression levels of PI3Kand p-Akt in AT1-AA positive group were significantly decreased than those in AT1-AA negative group(P0.05).Conclusion AT1-AA may be involved in the pathophysiology of cardiac hypertrophy in hyperthyroidism by activating PI3K/Akt signaling pathway through AT1R.

Effect of experimental hyperthyroidism on the maximum acute exercise tolerance and neuromuscular performance in rats

Background Thyroid hormones regulate many physiologic functions such as energy and heat production, synthesis of proteins, and muscle contraction. Objective This study aims to demonstrate the mechanism by which hyperthyroidism affects neuromuscular performance and acute exercise tolerance and whether this effect is reversible or not after recovery in rats. Materials and methods Rats used in this study were divided into three groups, each containing 10 rats: (a) in the euthyroid group, rats were selected by measurement of serum FT3 (triiodothyronin), FT4 (tetraiodothyronine), and thyroid-stimulating hormone levels. (b) In the hyperthyroid group, hyperthyroidism was induced by Eltroxin in increasing doses, beginning from 50 μg to reach 200 μg/kg body weight daily by intragastric administration for 3 weeks. (c) In the recovery group, hyperthyroid rats are allowed to recover by exogenous thyroxine withdrawal for 25 days. After induction, body weight and the maximal swimming time were estimated, and then retro-orbital blood samples were collected for estimation of malondialdehyde and the total antioxidant capacity. Rats were then killed by cervical decapitation. Phrenic nerve diaphragm preparations were excised, connected to a four-channel oscillograph for measuring the strength of muscle contraction at the start of the experiment and after 30 min activity using both direct and indirect stimulation. Glucose uptake by the muscle during 30 min of activity and 30 min of recovery was estimated. Results The data show that hyperthyroidism induced by Eltroxin elevates serum malondialdehyde significantly when compared with the euthyroid group, whereas reduces total antioxidant capacity significantly. Hyperthyroidism was also associated with reduction of body weight, the maximal swimming time, the strength of skeletal muscle contraction induced by direct and indirect repetitive stimulation, and its glucose uptake. Conclusion Oxidative stress plays a critical role in the pathogenesis of hyperthyroidism, especially on skeletal muscle performance and exercise tolerance. This effect is reversible after restoration of the euthyroid state.

Increased Serca Pump Expression is Associated with Slow Termination of Calcium Sparks and Delayed Local Recovery in Vascular Smooth Muscle Cells of Hyperthyroid Rats

In vascular smooth muscle cells of cerebral arteries (VSMCs), spontaneous and repetitive local Ca2+ signals produced by the Ca2+ channel/Ryanodine Receptor (RyRs), known as Ca2+ sparks, are involved in the regulation of vascular myogenic tone. However, the molecular mechanisms behind the frequency and properties of Ca2+ sparks in VSMCs are still under study. Considering that in VSMCs, spontaneous Ca2+ sparks are generated at preferred subcellular locations, we have analyzed the spatio-temporal properties of repetitive same-location Ca2+ sparks, its time-dependent recovery (or restitution) and the regulation that luminal Ca2+ might exert in this phenomenon by using the experimental model of hyperthyroid rat (T3).Ca2+ sparks recorded in VSMCs from T3 rats showed similar frequency, amplitude, and Ca2+ flux compared with those recorded in control cells. However, Ca2+ spark properties such as duration, size, time-to-peak, and k decay were significantly increased in T3 cells; and as a consequence, spark-mediated Ca2+ leak was augmented by 3.3-fold. In both experimental groups, amplitude recovery of repetitive Ca2+ sparks was an all-or-none phenomenon and did not show any time-dependency. Histogram distribution of spark-to-spark delays from T3 cells showed a 4-fold reduction in shorter delays (0-200 ms), with the shortest spark-to-spark delay of 115.9 ms in T3 cells and of 67.2 ms in control cells. Although SERCA pump expression was increased in vascular tissue from T3 rats, both basal Ca2+ concentration and intracellular SR Ca2+ load, determined by caffeine, remained unchanged. Our data suggest that in VSMCs of T3 rats spontaneous Ca2+ sparks decrease SR Ca2+ content not only by increasing its frequency but also by delaying its termination to counteract SR Ca2+ overload resulting from the overexpression of SERCA pump.