Rat Thyroid Research Articles

Effect of perinatal exposure to glyphosate and its mixture with 2,4-D and dicamba on rat dam kidney and thyroid function and offspring's health

The increasing use of the herbicide mixture of glyphosate, dicamba and 2-4-D to deal with glyphosate-resistant weeds raises concerns regarding human health and environmental risks. This study aimed to evaluate the effects of developmental exposure to glyphosate and a herbicide mixture containing glyphosate, dicamba and 2-4-D on rat dams' kidney and thyroid function and offspring's health. Pregnant Wistar rats were exposed from day-6 of gestation till weaning to regulatory relevant doses of glyphosate corresponding to the European Union (EU) acceptable daily intake (ADI; 0.5 mg/kg bw/day), and the no-observed-adverse-effect level (NOAEL; 50 mg/kg bw/day), and to a mixture of glyphosate, dicamba and 2,4-D all at the EU ADI (0.5, 0.002 and 0.3 mg/kg bw/day) respectively. After weaning the dams were sacrificed and blood and organs were collected. The pups' health was assessed by measuring viability, gestational and anogenital indices. Perinatal exposure to GLY alone and the herbicide mixture resulted in anti-androgenic effects in male offspring. In dams, exposure to glyphosate resulted in kidney glomerular and tubular dysfunction as well as increased thyroid hormone levels in a dose-dependent manner. Furthermore, exposure to the herbicide mixture resulted in effects similar to those observed with glyphosate at the NOAEL, suggesting at least an additive effect of the herbicide mixture at doses individually considered safe for humans.

Subchronic intraperitoneal toxicity of Sio2NPs on body weight and thyroid gland hormones in female Rats

This study investigated the toxicity effect of Sio2NPs on body weight and thyroid gland in female rats; the experiment was included. The experimental animals were randomly divided into three groups, including two treatment groups ( treated with a low dose (25mg/Kg ) and high dose (100mg/Kg of body weight) of sio2 NPs and one group as a control. Each group of them was divided into three subgroups according to the injection periods of exposure (10, 20, and 30) days daily, then measure the body weight and Thyroid function hormones (T3, T4, TSH), the results showed that there was a significant decrease (p<0.05) in the body weight of animals that exposed to SiO2 NPs at two doses (25 and 100 mg/kg) during (10 days) while increased during (20, 30 days) but the highest value recorded in the animals that were treated for (30 days) at both doses. On the other side, the T3 findings recorded a significant decrease (p< 0.05) for the animals that exposed to SiO2 NPs at low and high doses (25 and 100 mg/kg) (during (10 days) when compared with the control group As well as, there was a significant decrease (p< 0.05) in the level of T3 for all animals that treated with these doses during (20 and 3 days) in serum of animals that were treated with both doses of SiO2 NPs when compared with the control group (p< 0.05), while T4 showed s decreasing in the treated group during (10 and 20, 30 days) compared to a control group with highly significant ((p< 0.05), finally while TSH showed a highly increasing in treated group during (10 and 20, 30 days) compared to control group (p< 0.05). The study revealed that Exposure to Sio2NPs at different concentrations caused structural and functional and in the thyroid gland, characterized decrease in T3 and T4 hormone levels and an increase in the TSH hormone level and caused hypothyroidism This led to a decrease in the metabolism process and thus the body weight of animals gained a significant increase. Keywords: nanoparticles, Sio2NPs, Thyroid gland, T3, T4, TSH, Body weight, female rats.

Personalized CFTR Modulator Therapy for G85E and N1303K Homozygous Patients with Cystic Fibrosis.

CFTR modulator therapy with elexacaftor/tezacaftor/ivacaftor (ETI) has been approved for people with CF and at least one F508del allele in Europe. In the US, the ETI label has been expanded to 177 rare CFTR mutations responsive in Fischer rat thyroid cells, including G85E, but not N1303K. However, knowledge on the effect of ETI on G85E or N1303K CFTR function remains limited. In vitro effects of ETI were measured in primary human nasal epithelial cultures (pHNECs) of a G85E homozygous patient and an N1303K homozygous patient. Effects of ETI therapy in vivo in these patients were assessed using clinical outcomes, including multiple breath washout and lung MRI, and the CFTR biomarkers sweat chloride concentration (SCC), nasal potential difference (NPD) and intestinal current measurement (ICM), before and after initiation of ETI. ETI increased CFTR-mediated chloride transport in G85E/G85E and N1303K/N1303K pHNECs. In the G85E/G85E and the N1303K/N1303K patient, we observed an improvement in lung function, SCC, and CFTR function in the respiratory and rectal epithelium after initiation of ETI. The approach of combining preclinical in vitro testing with subsequent in vivo verification can facilitate access to CFTR modulator therapy and enhance precision medicine for patients carrying rare CFTR mutations.

Effect of different iodide intake during pregnancy and lactation on thyroid and cardiovascular function in maternal and offspring rats

ObjectiveWe aimed to investigate the impact of different iodide intake during pregnancy and lactation on iodine concentration in urine and serum, fatty acid metabolism, thyroid and cardiovascular function in maternal and offspring rats. MethodsPregnant rats were randomly assigned to four groups: normal adult iodide intake (NAI, 7.5 μg/d), normal pregnant iodide intake (NPI, 12.5 μg/d), 5 times (5 HI, 62.5 μg/d) and 10 times higher-than-normal pregnant iodide intake (10 HI, 125 μg/d). The maternal rats were continuously administered potassium iodide until postnatal day 16 (PN16). Thyroid function was measured by enzyme-linked immunosorbent assay (ELISA). The iodine concentration in urine and serum were detected by inductively coupled plasma mass spectrometry (ICP-MS). The messenger ribonucleic acid (mRNA) expressions of Krüppel-like factor 9 (KLF9) and thioredoxin reductase 2 (Txnrd2) were measured using quantitative real-time polymerase chain reaction (RT-qPCR). Characteristic distribution of KLF9 expression and its interaction with TRβ was assessed by immunohistochemical and immunofluorescence staining. Serum fatty acids were analyzed by Liquid Chromatography-Mass Spectrometry (LC-MS). Cardiac function and blood pressure were measured by echocardiography and a non-invasive tail-cuff system. ResultsHigh iodide intake (5 HI and 10 HI) during pregnancy and lactation results in increased urinary iodine concentration (UIC), serum total iodine concentration (STIC) and serum non-protein-bound iodine concentration (SNBIC) in both maternal and offspring rats, along with significantly increased FT3 and its target gene expression of KLF9. In maternal rats of both 5 HI and 10 HI groups, systolic blood pressure (SBP) was significantly higher, the increased SBP was significantly correlated with the increased UIC (r = 0.968, p = 0.002; r = 0.844, p = 0.035), KLF9 (r = 0.935, p = 0.006; r = 0.954, p = 0.003) and the decreased Txnrd2 (r = −0.909, p = 0.012; r = −0.912, p = 0.011). In maternal rats of 10 HI group, cardiac hyperfunction with increased LVEF, LVFS and decreased LVESD were observed. The increased LVEF and decreased LVESD were significantly correlated with UIC, STIC and SNBIC (r = 0.976, p = 0.001; r = 0.945, p = 0.005; r = 0.953, p = 0.003; r = −0.917, p = 0.01; r = −0.859, p = 0.028; r = −0.847, p = 0.033), LVEF, LVFS and LVESD were significant correlated with KLF9 (r = 0.950, p = 0.004; r = 0.963, p = 0.002; r = −0.990, p = 0.0002) and Txnrd2 expression (r = −0.979, p = 0.001; r = −0.915, p = 0.01; r = 0.933, p = 0.007), and the decreased LVESD was correlated with decreased epoxyeicosatrienoic acid (EET) metabolites: 5,6-EET, 8,9-DHET and 11,12-DHET (r = 0.999, p = 0.034; r = 1.000, p = 0.017; r = 1.000, p = 0.017). While in offspring rats, no significant change in SBP and cardiac function was found. STIC and SNBIC were much lower than those in maternal rats, and eicosapentaenoic acid (EPA) metabolites (9-HEPE, 15-HEPE and 14,15 DiHETE) were significantly increased. ConclusionIn addition to thyroid hormones, STIC, SNBIC, KLF9, Txnrd2, EET and EPA metabolites might be promising biomarkers in high iodide intake-induced thyroid and cardiovascular function.

Sesquiterpene lactones improve secretory diarrhea symptoms by inhibiting intestinal Ca2+-activated Cl– channel activities directly and indirectly

Secretory diarrhea caused by bacteria and viruses is usually accompanied by activation of the cystic fibrosis transmembrane conductance regulator (CFTR) and calcium-activated Cl– channels (CaCCs) in the intestinal epithelium. Inhibition of CFTR and CaCCs activities significantly reduces fluid losses and intestinal motility in diarrheal diseases. For this reason, CFTR and CaCCs are potential targets of therapeutic drug screening. Here, we reported that the sesquiterpene lactones, alantolactone (AL) and isoalantolactone (iAL), significantly inhibited ATP and Eact-induced short-circuit currents in T84, HT-29 and Fischer rat thyroid (FRT) cells expressing transmembrane protein 16A (TMEM16A) in a concentration-dependent manner. AL and iAL also inhibited the CaCC-mediated short-circuit currents induced by carbachol in the mouse colons. Both compounds inhibited forskolin-induced currents in T84 cells but did not significantly affect mouse colons. In vivo studies indicated that AL and iAL attenuated gastrointestinal motility and decreased watery diarrhea in rotavirus-infected neonatal mice. Preliminary mechanism studies showed that AL and iAL inhibited CaCCs at least partially by inhibiting Ca2+ release and basolateral membrane K+ channels activity. These findings suggest a new pharmacological activity of sesquiterpene lactone compounds that might lead to the development of treatments for rotaviral secretory diarrhea.

Assessing the Influence of Propylthiouracil and Phenytoin on the Metabolomes of the Thyroid, Liver, and Plasma in Rats.

The thyroid hormones (THs) regulate various physiological mechanisms in mammals, such as cellular metabolism, cell structure, and membrane transport. The therapeutic drugs propylthiouracil (PTU) and phenytoin are known to induce hypothyroidism and decrease blood thyroid hormone levels. To analyze the impact of these two drugs on systemic metabolism, we focused on metabolic changes after treatment. Therefore, in a rat model, the metabolome of thyroid and liver tissue as well as from the blood plasma, after 2-week and 4-week administration of the drugs and after a following 2-week recovery phase, was investigated using targeted LC-MS/MS and GC-MS. Both drugs were tested at a low dose and a high dose. We observed decreases in THs plasma levels, and higher doses of the drugs were associated with a high decrease in TH levels. PTU administration had a more pronounced effect on TH levels than phenytoin. Both drugs had little or no influence on the metabolomes at low doses. Only PTU exhibited apparent metabolome alterations at high doses, especially concerning lipids. In plasma, acylcarnitines and triglycerides were detected at decreased levels than in the controls after 2- and 4-week exposure to the drug, while sphingomyelins and phosphatidylcholines were observed at increased levels. Interestingly, in the thyroid tissue, triglycerides were observed at increased concentrations in the 2-week exposure group to PTU, which was not observed in the 4-week exposure group and in the 4-week exposure group followed by the 2-week recovery group, suggesting an adaptation by the thyroid tissue. In the liver, no metabolites were found to have significantly changed. After the recovery phase, the thyroid, liver, and plasma metabolomic profiles showed little or no differences from the controls. In conclusion, although there were significant changes observed in several plasma metabolites in PTU/Phenytoin exposure groups, this study found that only PTU exposure led to adaptation-dependent changes in thyroid metabolites but did not affect hepatic metabolites.

Electronic microscopic features of parafollicular cells of rat's thyroid gland after 60 days introduction of tartrazine and Mexidol®

Objective: To establish the effect of the administration of tartrazine for 60 days, as well as Mexidol® under these conditions, on the structural features of the parafollicular cells of the rat's thyroid gland at the electron microscopic level. Material and methods. Thirty white male rats weighing 200-210 g were divided into five groups six rats each. The Group I is the control; the Groups II and III — rats received tartrazine at a concentration of 750 and 1500 mg/kg for 60 days; the Groups IV and V — under similar conditions Mexidol® was administered at the rate of 50 mg/kg. Qualitative changes in parafollicular cells were studied using electron microscopy, and quantitative changes — by morphometry Results. The fine-grained or fibrous contents were detected in the cisterns of the rough endoplasmic reticulum, and areas of the destroyed matrix in some mitochondria after exposure to tartrazine. The ratio of area eu-chromatin/heterochromatin decreased in the Groups II and III by 5.7% and 56.9%, respectively, and the diameter of secretory granules — by 12.3% and 19%, respectively, compared with the Group I. The ratio of area euchromatin/het-erochromatin increased by 79.6% in Group V, and diameter of secretory granules — by 8.2% and 6.5% in the Groups IV and V respectively, compared with the data of the Groups II and III. Conclusions. The introduction of tartrazine in different doses for 60 days causes dose-dependent qualitative and quantitative changes in the ultrastructure of parafollicular cells, and the introduction of Mexidol® against this background causes a decrease in their severity.

Micromorphometric parameters of the thyroid gland and antioxidant status in rats with acute radiation damage against the background of the use of DAFS-25 and MONCLAVIT-1

The search for formulations of radioprotective agents with different mechanisms of action is one of the promising areas in radiobiology. One of the components of the body's antioxidant system are glutathione peroxidases, selenium-dependent proteins capable of neutralizing reactive oxygen species and inhibiting lipid peroxidation. In addition, selenium is involved in the metabolism of thyroid hormones and the maintenance of cellular homeostasis of thyrocytes. The thyroid gland is involved in the regulation of metabolism, and also affects the functioning of many body systems. Consequently, the course and outcome of radiation pathology will depend on the functional state of the thyroid gland. Iodine is required for the synthesis of thyroid hormones. DAFS-25 is a feed additive for farm animals containing diacetophenonyl selenide (mass fraction of selenium is 25%). Monclavit-1 is a veterinary drug containing iodine in the form of a polymer complex. The combined use of selenium and iodine as a radioprotective agent is currently poorly understood. Thus, the purpose of this work was to evaluate changes in the concentration of malondialdehyde and the functional state of the thyroid gland in acute radiation injury against the background of the use of DAPS-25 and Monclavit-1.In order to conduct the experiment on the principle of pairs of analogues, 5 groups of animals were formed, 10 individuals each. The determination of the concentration of malondialdehyde was carried out by the colorimetric method. The material selected for histological examination was fixed in a formalin solution, then dehydrated, paraffinized, and stained with hematoxylin-eosin.The use of DAFS-25 and Monclavit-1 contributes to a decrease in the concentration of malondialdehyde in the blood of irradiated animals and a relative restoration of the histological structure of the thyroid gland on the 30th day of the experiment.

P079 Personalized CFTR modulator therapy for G85E and N1303K homozygous patients with cystic fibrosis

Objectives: The cystic fibrosis (CF) transmembrane conductance regulator (CFTR) modulators elexacaftor/tezacaftor/ivacaftor (ETI) are approved for people with CF (pwCF) and at least one F508del-allele in Europe. In the US, ETI label was expanded by >100 rare CFTR mutations responsive in fisher rat thyroid cells, including G85E, but not N1303K. However, the effect of ETI on G85E or N1303K CFTR proteins is unknown.

The transcription factors Creb1 and CEBPB regulate Sox9 promoter activity in TM4 Sertoli cells

In Sertoli cells, the Sox9 gene is essential for testicular development and normal spermatogenesis. SOX9 is critical for postnatal Sertoli cells differentiation and proliferation in the testis. However, the molecular mechanisms that specifically regulate its expression are not entirely understood. Sox9 expression is regulated by CREB1 and CEBPB in other biological contexts such as during chondrogenesis and in rat thyroid follicular cells. We hypothesized that Sox9 promoter activity is regulated by CREB1 and CEBPB in Sertoli cells. Our results show that Sox9 expression is dependent on the activation of these transcription factors by the cAMP/PKA signaling pathway in TM4 Sertoli cells. Chromatin immunoprecipitation and promoter/reporter luciferase assays with 5′ promoter deletions and site-directed mutagenesis demonstrated that CREB1 is being recruited to a DNA regulatory element at -141 bp of the Sox9 promoter region. Such regulation is dependent on the cAMP/PKA signaling pathway, resulting in phosphorylation of CREB1. Activation of Sox9 expression by CEBPB may involve its recruitment to the proximal promoter region by protein–protein interaction with CREB1. Thus, we have shown that the Sox9 promoter is being regulated by the transcription factors CREB1 and CEBPB in TM4 Sertoli cells and involve their recruitment to the proximal promoter region.

Retromer involvement in trafficking of the calcium-activated K channel, KCa3.1

The intermediate-conductance Ca 2+ -activated K + channel KCa3.1 ( KCNN4) regulates many physiological processes, including, water and electrolyte transport in polarised epithelia and vascular tone. Crucial for KCa3.1 function is the regulation of the number of channels at the plasma membrane. Even though, the mechanism of trafficking of KCa3.1 to and from the basolateral membrane (BLM) of epithelial cells has been advanced recently, there is opposing evidence suggesting that KCa3.1 is recycled back to the leading edge of migrating cells; while others have reported that KCa3.1 does not enter recycling endosomes, but is targeted for degradation. The highly conserved multi-protein complex Retromer has been demonstrated to regulate the membrane retrieval and recycling of many membrane-bound proteins, including ion channels. Using mass-spectrometry, it was reported that when VPS35, a core protein of the Retromer complex, was knocked-down, the membrane expression of KCa3.1 was reduced 1.4 fold in HeLa cells; suggesting a link between Retromer and trafficking of KCa3.1. In contrast, our data indicate KCa3.1 was not affected by knockdown of VPS35 in our FRT (Fischer rat thyroid)-KCa3.1 stable cell line. Here, we have examined other key components (sorting nexins SNX1, SNX4, SNX27; cargo binding proteins) of the Retromer complex to determine if those proteins aid in trafficking of KCa3.1 directly to the BLM. We conducted immunoblot and Ussing chamber experiments to examine the effects of knockdown of SNX 1, SNX2 or SNX27 on the BLM population of KCa3.1 and functional expression of the channel (K + current), respectively. Using our FRT-KCa3.1 cell line, we demonstrate knockdown of SNX1, SNX4 or SNX27 decreases KCa3.1 current. Further, we demonstrate knockdown of SNX4 or SNX27 decreases BLM expression of KCa3.1, consistent with the decrease in current observed.These data, along with our previous data, strongly indicate that the role of Retromer in the trafficking of KCa3.1 to the BLM of epithelial cells is quite dynamic. Reducing SNX4 or SNX27 have notable effects on trafficking of KCa3.1. While knockdown of SNX1 might affect the trafficking of KCa3.1 by altering other proteins of the Retromer complex. This work was supported by the National Institutes of Health grants HL083060 and HL092157 to DCD, Lottery Health New Zealand (R-LHR-2019-101706) to FJM, Aim Fund grant to KLH, and the Department of Physiology, University of Otago. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

The exocyst complex is required for the trafficking and delivery of KCa3.1 to the basolateral membrane of polarized epithelia.

Control of the movement of ions and water across epithelia is essential for homeostasis. Changing the number or activity of ion channels at the plasma membrane is a significant regulator of epithelial transport. In polarized epithelia, the intermediate-conductance calcium-activated potassium channel, KCa3.1 is delivered to the basolateral membrane where it generates and maintains the electrochemical gradients required for epithelial transport. The mechanisms that control the delivery of KCa3.1 to the basolateral membrane are still emerging. Herein, we investigated the role of the highly conserved tethering complex exocyst. In epithelia, exocyst is involved in the tethering of post-Golgi secretory vesicles with the basolateral membrane, which is required before membrane fusion. In our Fisher rat thyroid cell line that stably expresses KCa3.1, siRNA knockdown of either of the exocyst subunits Sec3, Sec6, or Sec8 significantly decreased KCa3.1-specific current. In addition, knockdown of exocyst complex subunits significantly reduced the basolateral membrane protein level of KCa3.1. Finally, co-immunoprecipitation experiments suggest associations between Sec6 and KCa3.1, but not between Sec8 and KCa3.1. Collectively, based on these data and our previous studies, we suggest that components of exocyst complex are crucially important in the tethering of KCa3.1 to the basolateral membrane. After which, Soluble N-ethylmaleimide-sensitive factor (SNF) Attachment Receptors (SNARE) proteins aid in the insertion of KCa3.1-containing vesicles into the basolateral membrane of polarized epithelia.NEW & NOTEWORTHY Our Ussing chamber and immunoblot experiments demonstrate that when subunits of the exocyst complex were transiently knocked down, this significantly reduced the basolateral population and functional expression of KCa3.1. These data suggest, combined with our protein association experiments, that the exocyst complex regulates the tethering of KCa3.1-containing vesicles to the basolateral membrane prior to the SNARE-dependent insertion of channels into the basolateral membrane of epithelial cells.

Short-term toxicity assessment of combined use of Zidovudine, Lamivudine, and Lopinavir/Ritonavir in vitro and in vivo.

A combination of zidovudine (AZT), lamivudine (3TC), and lopinavir/ritonavir (LPV/r) is one of the most effective drugs for preventing mother-to-child transmission (PMTCT) of HIV. However, limited information is available regarding its systemic toxicity. This study aimed to investigate its potential toxicity. An acute oral toxicity test was conducted to assess the potential acute toxicity of AZT + 3TC + LPV/r. Bacterial reverse mutation, mammalian erythrocyte micronucleus, and mouse spermatogonia chromosomal aberration tests were conducted to assess its potential genotoxicity. A 28-day feeding test was conducted to assess the potential subacute toxicity. In mice, the LD50 of the AZT + 3TC + LPV/r mixture was greater than 2000 mg/kg body weight (BW). The rate of micronucleated polychromatic erythrocytes (PCEs) increased in a dose-dependent manner in mice (P<0.01). After treatment with AZT + 3TC + LPV/r for 28 days, the BW gain of male and female rats in the high-dose group was lower than that in the control group (P<0.05); the relative weights of the liver, kidney, spleen, and brain increased (P<0.05); and pathological abnormalities appeared in the thyroid and spleen of male and female rats in the high-dose group. The hemoglobin (HGB) and red blood cells (RBCs) count in male and female rats decreased, but the white blood cells (WBCs) and lymphocyte apoptosis rates in male and female rats in the high-dose group increased (P<0.05). The total protein, albumin, cholesterol, and blood glucose levels of male and female rats in the high-dose group were significantly decreased (P<0.05). The alanine aminotransferase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), creatinine (Cr) and blood urea nitrogen (BUN) levels of male and female rats in the medium- and high-dose groups increased significantly (P<0.05). The results suggest that AZT + 3TC + LPV/r may exhibit genotoxicity and subacute toxicity under experimental conditions.

Protective Effects of Quercetin and Phytic Acid (Myo Inositol) on Cadmium Toxicity in Thyroid Gland of Albino Rats

Protective Effects of Quercetin and Phytic Acid (Myo Inositol) on Cadmium Toxicity in Thyroid Gland of Albino Rats

Assessment of the Protective Effects of Selenium and Zinc against Potassium Dichromate Induced Thyrotoxicity in Preimplanted &lt;i&gt;Wistar albinos&lt;/i&gt; Rats

Hexavalent chromium is an environmental pollutant considered to be an endocrine-disrupting metal. Selenium and zinc are essential trace elements, known to play a crucial role in thyroid homeostasis. The purpose of the current work is to investigate the effects of potassium dichromate (K₂Cr₂O7) administrated subcutaneously (s.c) on the 3rd day of pregnancy in preimplanted rats by using graded doses (10, 50, 100 mg/kg, s.c) or K₂Cr₂O7 (10 mg/kg, s.c) in association with Selenium (0.3 mg/kg, s.c) and Zinc chloride (20 mg/kg, s.c). The hormonal profile, apoptosis induction and histological changes in thyroids were evaluated. Our main findings showed that K₂Cr₂O7 promoted hypothyroidism with a significant decrease in plasma T3 and T4 levels (P&lt;0.001), while plasma TSH level increased significantly (P&lt;0.001), in addition, a hypertrophy of the thyroid was noted (P&lt;0.01). Moreover, K2Cr2O7 (10 mg/kg, s.c) induced apoptosis via the caspase 3 pathway (P&lt;0.001) and altered the gland histoarchitecture. The co-treatment with Se or ZnCl₂ has ameliorated the hormonal status and restored partially the thyroid histoarchitecture. We concluded that the administration of Selenium and Zinc can prevent the hazardous effects of potassium dichromate on the hormonal and histological status of the thyroid gland in preimplanted Wistar albino rats.

The possible protective role of vitamin C versus melatonin on potassium dichromate induced changes in rat thyroid gland: light and electron microscopic study

ABSTRACT Potassium dichromate is widely used in various laboratory and industrial applications. Vitamin C and melatonin are well-known antioxidants. Study the microscopic and morphometric alterations in the thyroid gland in adult male albino rats after the administration of potassium dichromate for successive 2 months and also to assess the possible protective effect of vitamin C versus melatonin on these changes. Sixty adult male albino rats were randomly divided into four main groups. Group I (The control group). Group II received potassium dichromate (25 mg/kg/day) dissolved in distilled water by intraperitoneal (i.p) injection for 2 months. Group III received the same dose of potassium dichromate with vitamin C (120 mg/kg/day) orally through an intragastric intubation. Group IV received the same dose of potassium dichromate and melatonin (10 mg/kg/day) as an i.p injection. Thyroid gland samples were prepared for light and electron microscopic studies. Potassium dichromate group demonstrated congested blood vessels, follicular hyperplasia, follicular enlargement with degenerated lining cells that were exfoliated in the lumen. The parafollicular cells appeared with darkly stained nuclei. PAS reaction showed weak reaction in the colloid with an abnormal pattern of vacuolization. A highly significant increase in the percentage area of fibrosis was detected in Mallory trichrome sections. Ultrastructurally, follicular cells and parafollicular cells appeared irregular in shape with dark, small heterochromatic nuclei. Small, electron-dense granules in the parafollicular cells were found. Potassium dichromate and vitamin C-treated group III showed partial improvement of the thyroid gland. The PAS reaction showed that nearly all the follicles were more or less similar to those of the control group. A significant decrease in the percentage area of fibrosis in group III was found as compared to those in group II. Potassium dichromate and melatonin-treated group showed that the thyroid gland was nearly similar to that of the control group. Vitamin C and melatonin could partially protect against potassium dichromate induced changes in the thyroid gland and the protective effect of melatonin was better than that of vitamin C.

Dynamic changes in the histomorphological structure of the thyroid gland of rats against the background of experimental autoimmune thyroiditis

In preclinical studies, which are conducted to study the therapeutic effectiveness and pharmacological safety of biologically active compounds for the correction of autoimmune thyroiditis, various experimental models of this pathology are used in the experiment.&#x0D; In this work, we analyzed various models of thyroiditis that have been used for the past fifty years. Such an analysis made it possible to choose the most optimal model for the study of autoimmune pathology of the thyroid gland as well as for the correction of this condition. The analysis of known and the search for new pathogenetically justified models of autoimmune diseases of endocrine organs is a very urgent task.&#x0D; The aim of the work was to study the dynamics of changes in the histomorphological structure of the thyroid gland when modeling autoimmune thyroiditis in rats using an allogeneic antigen isolated from the human thyroid gland.&#x0D; The postoperative thyroid gland of a person was used as an antigen. Morphological changes in the thyroid gland were studied one, three and six months after the end of the simulation.&#x0D; It was found that the use of this type of immunization led to changes in the parenchyma of the gland, characteristic of autoimmune thyroiditis. Already one month after modeling, Gürtle cells, fibrosis, areas of lymphoid infiltration of the parenchyma were registered. These pathological changes persisted and worsened three and six months after the end of the simulation.&#x0D; The investigated type of model of experimental autoimmune thyroiditis is easily reproduced. Pathological changes in the gland deepen over time and are comparable to those that occur in people with Hashimoto's thyroiditis

TOXIC EFFECTS OF AROCLOR 1254 ON RAT HEART AND THYROID AND MODIFYING ROLE OF SELENIUM STATUS

Objective: Polychlorinated biphenyls (PCBs) were very widely used in industrial products in past. These chemicals were banned in the 1970s due to their toxic effects. PCBs can still affect human health, as they are persistent in the environment. Aroclor 1254 (A1254) is a commercial PCB congener which was used in electrical transformers, fluorescent lighting fixtures and old appliances such as televisions or refrigerators. In this study, we aimed to evaluate the toxic effects of A1254 on heart and thyroid in male Sprague-Dawley rats. In addition, the modifying role of selenium status was also evaluated.&#x0D; Material and Method: 8-week-old male Sprague-Dawley (SD) rats were used in the experiment. The animals were separated randomly into 6 groups (n=6) as control; selenium supplemented (SeS); selenium deficient (SeD); A1254 exposed (A); selenium supplemented A1254 exposed (ASeS) and selenium deficient A1254 exposed (ASeD). A1254 was applied by gavage during the last 15 days of feeding period. Heart and thyroid weights and relative weights, plasma thyroid hormone levels, as well as thyroid and heart tissue oxidative/antioxidative parameters were evaluated.&#x0D; Result and Discussion: Results showed that A1254 exposure and selenium deficiency caused oxidative stress on both heart and thyroid. Plasma fT3 and fT4 levels markedly changed in ASeD group. In conclusion, it can be stated that A1254 exposure can cause lead to oxidative/antioxidative imbalance in both thyroid and heart and can disrupt functioning of thyroid hormones. Selenium seems to have a modifying role in A1254 toxicity in both organs, the importance of which should be evaluated with further mechanistic experiments.

Microcystin-LR induced transgenerational effects of thyroid disruption in zebrafish offspring by endoplasmic reticulum stress-mediated thyroglobulin accumulation and apoptosis

MC-LR can interfere with thyroid function in fish, but the underlying mechanism is still unclear. Current study focuses to study the intergenerational inheritance of MC-LR-induced thyroid toxicity in zebrafish and in rat thyroid cells. In vivo experiments, adult female zebrafish (F0) were exposed to MC-LR (0, 5, and 25 μg/L) for 90 days and mated with male zebrafish without MC-LR exposure to generate F1 generation. F1 embryos were allowed to develop normally to 7 days post-fertilization (dpf) in clear water. In the F0 generation, MC-LR induced disturbance of the hypothalamic-pituitary-thyroid (HPT) axis, leading to a decrease in the production of thyroid hormones. Maternal MC-LR exposure also induced growth inhibition by altering thyroid hormones (THs) homeostasis and interfering with thyroid metabolism and development in F1 offspring. Mechanistically, MC-LR caused excessive accumulation of ROS and induced ER stress that further lead to activation of UPR in the F0 and F1 offspring of zebrafish. Interestingly, our findings suggested that MC-LR exposure hampered thyroglobulin turnover by triggering IRE1 and PERK pathway in zebrafish and FRTL-5 thyroid cells, thus disturbing the thyroid endocrine system and contributing to the thyroid toxicity from maternal to its F1 offspring of zebrafish. Particularly, inhibition of the IRE1 pathway by siRNA could alleviate thyroid development injury induced by MC-LR in FRTL-5 cells. In addition, MC-LR induced thyroid cell apoptosis by triggering ER stress. Taken together, our results demonstrated that maternal MC-LR exposure causes thyroid endocrine disruption by ER stress contributing to transgenerational effects in zebrafish offspring.

Effects of 60-day sodium benzoate exposure on the ultramicroscopic structure of rat's thyroid gland follicular cells

Effects of 60-day sodium benzoate exposure on the ultramicroscopic structure of rat's thyroid gland follicular cells