Plasma Thyroid Hormone Research Articles

Association of thyroid hormones with the severity of chronic kidney disease: a cross-sectional observational study at Tabuk, Saudi Arabia.

The interplay between chronic kidney disease (CKD) and thyroid dysfunction is becoming more evident in the biomedical community. However, the intricacies of their relationship warrant deeper investigation to understand the clinical implications fully. This study aims to systematically evaluate the correlation between thyroid hormone levels, including thyroid-stimulating hormone (TSH), triiodothyronine (T3), and thyroxine (T4), and markers of renal disease severity. These markers include serum creatinine, urea, and parathyroid hormone (PTH) levels in individuals diagnosed with CK). We conducted a cross-sectional observational study involving a cohort of 86 participants with CKD recruited from the renal clinic at King Fahad Hospital in Tabuk. Biochemical parameters, encompassing plasma electrolytes and thyroid hormone concentrations, were quantitatively assessed. These measurements were performed with the aid of a Roche Cobas E411 analyzer. The Pearson correlation coefficient was employed to delineate the strength and direction of the associations between the thyroid function markers and renal disease indicators. The statistical analysis highlighted a generally weak correlation between the concentrations of thyroid hormones and the indicators of renal disease severity, with Pearson correlation coefficients between -0.319 and 0.815. Critically, no significant correlation was found between creatinine and thyroid hormones (TSH, T3, T4), nor was any substantial correlation between urea and thyroid hormones. Conversely, a robust positive correlation was noted between the levels of parathyroid hormone and serum creatinine (r=0.718, p<0.001). The data suggests that thyroid hormone levels have a minimal correlation with the severity of renal disease markers. In contrast, the pronounced correlation between PTH and creatinine underscores the importance of considering PTH as a significant factor in managing and therapeutic intervention of CKD complications. These initial findings catalyze further research to thoroughly investigate the pathophysiological relationships and potential therapeutic targets concerning thyroid dysfunction in patients with renal impairment.

Triiodothyronine (T3), but not resting metabolic rate correlates positively with per- and polyfluoroalkyl substances (PFAS) in Arctic terns

In Arctic seabirds, positive correlations between per- and polyfluoroalkyl substances (PFAS) and thyroid hormones (THs) and resting metabolic rate (RMR) have been documented. Herein we investigated levels and patterns of PFAS in Arctic terns (Sterna paradisaea) nesting in Kongsfjorden, Svalbard (Norway), and if circulating concentrations of PFAS correlated with their circulating concentrations of TH and the RMR of the birds. The hypothesis was that there will be positive correlations between PFAS, TH, and RMR, indicating that PFAS-induced increases in plasma THs could be responsible for the increased RMR. The dominating PFAS in the terns were perfluorooctane sulfonate (PFOS), perfluoroundecanoate (PFUnDA) and perfluorotridecanoate (PFTrDA). The PFAS pattern was similar to what has been found in other seabirds in Kongsfjorden. There were positive correlations between several PFAS and total triiodothyronine (TT3) concentrations in the terns. When sex was accounted for there were significant correlations in female terns, but not in males. There were no correlations between PFAS and RMR or between TT3 and RMR. This indicates that there is no link between a PFAS-induced increase in plasma TT3 concentrations and a resultant increased RMR. The positive associations between blood PFAS concentrations and plasma TT3 concentrations may be a passive association, as both PFAS and T3 bind to thyroid hormone binding proteins (THBP). We recommend that interrelationships between circulating concentrations of PFAS, THs and THBP are investigated further to identify the role of PFAS as TH disrupting chemicals and chemicals that may affect the RMR in birds.

Prediction of gestational diabetes mellitus by multiple biomarkers at early gestation

BackgroundIt remains unclear which early gestational biomarkers can be used in predicting later development of gestational diabetes mellitus (GDM). We sought to identify the optimal combination of early gestational biomarkers in predicting GDM in machine learning (ML) models.MethodsThis was a nested case-control study including 100 pairs of GDM and euglycemic (control) pregnancies in the Early Life Plan cohort in Shanghai, China. High sensitivity C reactive protein, sex hormone binding globulin, insulin-like growth factor I, IGF binding protein 2 (IGFBP-2), total and high molecular weight adiponectin and glycosylated fibronectin concentrations were measured in serum samples at 11–14 weeks of gestation. Routine first-trimester blood test biomarkers included fasting plasma glucose (FPG), serum lipids and thyroid hormones. Five ML models [stepwise logistic regression, least absolute shrinkage and selection operator (LASSO), random forest, support vector machine and k-nearest neighbor] were employed to predict GDM. The study subjects were randomly split into two sets for model development (training set, n = 70 GDM/control pairs) and validation (testing set: n = 30 GDM/control pairs). Model performance was evaluated by the area under the curve (AUC) in receiver operating characteristics.ResultsFPG and IGFBP-2 were consistently selected as predictors of GDM in all ML models. The random forest model including FPG and IGFBP-2 performed the best (AUC 0.80, accuracy 0.72, sensitivity 0.87, specificity 0.57). Adding more predictors did not improve the discriminant power.ConclusionThe combination of FPG and IGFBP-2 at early gestation (11–14 weeks) could predict later development of GDM with moderate discriminant power. Further validation studies are warranted to assess the utility of this simple combination model in other independent cohorts.

Low Thyroid Hormones Level Attenuates Mitochondrial Dysfunction and Right Ventricular Failure in Pulmonary Hypertensive Rats.

This study is to investigate the repercussions of hypothyroidism in the pathophysiological progression of pulmonary arterial hypertension (PAH). While the control (CTL, n = 5) male Wistar rats received vehicle, PAH was induced with monocrotaline (MCT group, n = 15). Hypothyroidism was induced in a subset of rats by methimazole 3weeks prior to the MCT injection (MMZ + MCT group, n = 15). Plasma thyroid hormones were measured by radioimmunoassay. Electrocardiographic, echocardiographic, and hemodynamic analyses were performed to evaluate the progression of PAH. Gene expression of antioxidant enzymes and cardiac hypertrophy markers were assessed by qPCR. Mitochondrial respiration, ATP levels, and ROS production were measured in right ventricular (RV) samples. Plasma T3 and T4 decreased in both MCT and MMZ + MCT groups (p < 0.05). Right ventricular systolic pressure (RVSP) increased, and RV - dP/dt, + dP/dt, and contractility index decreased in the MCT versus the CTL group and remained within control levels in the MMZ + MCT group (p < 0.05). Relative RV weight, RV wall thickness, RV diastolic area, and relative lung weight were augmented in the MCT versus the CTL group, whereas all parameters were improved to the CTL levels in the MMZ + MCT group (p < 0.05). Only the MCT group exhibited an increased duration of QTc interval compared to the baseline period (p < 0.05). ADP-induced mitochondrial respiration and ATP levels were decreased, and ROS production was increased in MCT versus the CTL group (p < 0.05), while the MMZ + MCT group exhibited increased mitochondrial respiration versus the MCT group (p < 0.05). Hypothyroidism attenuated the RV mitochondrial dysfunction and the pathophysiological progression of MCT-induced PAH.

Magnitude and time course of urinary iodine excretion in patients after amiodarone therapy.

Amiodarone is a source of iodine excess that may persist in the body for long time after its withdrawal. The aim of the present analysis was to evaluate the magnitude and long-term time course of 24-h urinary iodine (UI) excretion in patients on antiarrhythmic therapy with amiodarone. 24-h UI excretion and thyroid function were evaluated in 67 patients on amiodarone therapy. All patients were clinically and biochemically euthyroid before starting treatment and were followed-up by 6-month measurements of 24-h UI excretion and plasma thyroid hormones levels. Upon amiodarone withdrawal, normal range of UI was achieved after a mean time of 15.2±7.7 months. Since amiodarone initiation, 20 patients developed thyroid dysfunction. No differences were observed in terms of treatment length or median UI levels between patients remaining euthyroid and those developing thyroid dysfunction: median UI in the euthyroid group was 8094 µg/24 h (Interquartile Range [IQR]: 4082-10766) vs. 10851 µg/24 h (IQR: 8529-12804) in the thyroid dysfunction group at 6 months (P=0.176) and 8651 µg/24 h (IQR: 6924-11574) vs. 8551 µg/24 h (IQR: 4916-13580) at one year from amiodarone initiation (P=0.886). The occurrence of thyroid dysfunction was equally distributed among patients taking amiodarone for more than one year versus those under treatment for less than one year. These results confirm the long-lasting total-body iodine stores and consequent excretion in patients after amiodarone withdrawal. These long-lasting iodine stores might be taken into special account in patients necessitating therapy with radioactive iodine and for long-term monitoring of thyroid function after amiodarone discontinuation.

Plasma Thyroid Hormone Concentration is Associated with Hepatic Triglyceride Content in Patients with Type 2 Diabetes

This cross-sectional study investigated the association between plasma thyroid hormone levels and hepatic triglyceride content in 150 patients with type 2 diabetes. Our findings revealed a significant negative correlation between plasma triiodothyronine (T3) levels and hepatic triglyceride content, suggesting a protective metabolic role of T3. No significant correlations were observed with thyroxine (T4) or thyroid-stimulating hormone (TSH). The study underscores the potential of T3 as a modulator of hepatic lipid metabolism in diabetic patients, highlighting its relevance in managing hepatic complications associated with diabetes. Further research is necessary to confirm these findings and explore therapeutic implications. Keywords: Thyroid Hormones, Hepatic Triglyceride, Type 2 Diabetes, Triiodothyronine (T3)

Thyroid hormone changes in critical surgical illness: a narrative review

The systemic response to stress caused by a critical surgical illness is characterized by a series of events that precede metabolic and neuroendocrine dysregulation. However, the relevance of theclassically described 'stress response' is now highly questionable in an era where profound physiological deconditioning is common in critically ill, surgical and non-surgical patients. Common assessment techniques do not accurately reflect the integrity of the hypothalamic-pituitary-thyroid axis in the course of a critical chronic disease state. The clinical presentation ismostly masked by symptoms of the underlying critical illness when plasma thyroid hormone concentrations are altered. The frequent development of multimorbidity in critically ill patients is the reason for the need for a more detailed analysis of the neuroendocrine model of activation. Basic scientific studies suggest that low levels of circulating thyroid hormones in the acute phase are an adaptive process, but the chronic condition could directly cause organ damage. Here, we review factors that have emerged to challenge the conventional model of euthyroid sick syndrome (ESS) in the surgically critically ill as an adaptive process, and suggest that the stage of the critical illness is an important consideration in the critically ill. Examining the stressresponse in the critically ill presents opportunities to improve outcomes through improved understanding of the neuroendocrine aspects.

Developmental toxicity of short-chain chlorinated paraffins on early-stage chicken embryos in a shell-less (ex-ovo) incubation system

Short-chain chlorinated paraffins (SCCPs) are listed as a category of globally controlled persistent organic pollutants (POPs) by the Stockholm Convention in 2017. However, SCCP toxicity, particularly their developmental toxicity in avian embryos, has not been well studied. In this study, we observed the early development of chicken embryos (Gallus gallus domesticus) by applying a shell-less (ex-ovo) incubation system developed in our previous studies. After exposing embryos at Hamburger Hamilton stage (HHS) 1 to SCCPs (control, 0.1% DMSO; SCCPs-L, 200 ng/g; SCCPs-M, 2000 ng/g; SCCPs-H, 20,000 ng/g), we observed the development of embryos from the 3rd to 9th incubation day. Exposure to SCCPs-M and -H induced a significant reduction in survival, with an LD50 of 3100 ng/g on the 9th incubation day. Significant dose-dependent decreases in body length were observed from days 4–9. We also found that SCCPs-H decreased the blood vessel length and branch number on the 4th incubation day. Additionally, SCCPs-H significantly reduced the heart rate on the 4th and 5th incubation days. These findings suggest that SCCPs may have potential of developmental and cardiovascular toxicity during the early stages of chicken embryos. Quantitative PCR of the mRNA of genes related to embryonic development showed that SLC16A10 (a triiodothyronine transporter) level decreased in the SCCPs-H group, showing a significant positive correlation with the body length of embryos. THRA level, a thyroid hormone receptor, was significantly decreased in the SCCPs-H group, whereas that of DIO3 level, a deiodinase was significantly increased. These results suggest that SCCPs exposure induces developmental delays via the thyroxine signaling pathway. Analysis of thyroid hormones (THs) in blood plasma also indicated a significant reduction in thyroxine (T4) levels in the SCCPs-H group on the 9th incubation day of embryos. In conclusion, SCCPs induce developmental toxicity by disrupting thyroid functions at the early-life stage of chicken embryos.

Plasmapheresis in thyrotoxicosis: a single-center case series

BackgroundPlasmapheresis represent an alternative therapeutic option for hyperthyroidism with thyroid storm or refractory cases. It provides a rapid decrease in plasma thyroid hormones and anti-thyroid antibodies. The aim of this paper was to report our single center’s experience in managing particular situations of hyperthyroidism using apheresis.Cases presentationThe following case series describes three young African patients (two females, one male) aged 29, 37, and 25 years old, respectively, with Graves’ disease who presented with drug ineffectiveness, drug-induced agranulocytosis, and thyroid storm with multi-organ failure. The three patients underwent plasmapheresis sessions leading to effective decline of thyroid hormone levels and offering a window for processing total thyroidectomy.Discussion/conclusionThe standard management of thyrotoxicosis and thyroid storm was usually codified by the concomitant use of antithyroid medication, iodine, beta-blockers, and corticosteroids. This medical preparation can be effective in most cases. However, drug toxicity or ineffectiveness can limit the use of such therapeutics. Our paper supports the efficiency and safety of therapeutic plasma exchange in the preoperative management of thyrotoxicosis.

Intestinal remodeling during Xenopus metamorphosis as a model for studying thyroid hormone signaling and adult organogenesis

Intestinal development takes places in two phases, the initial formation of neonatal (mammals)/larval (anurans) intestine and its subsequent maturation into the adult form. This maturation occurs during postembryonic development when plasma thyroid hormone (T3) level peaks. In anurans such as the highly related Xenopus laevis and Xenopus tropicalis, the larval/tadpole intestine is drastically remodeled from a simple tubular structure to a complex, multi-folded adult organ during T3-dependent metamorphosis. This involved complete degeneration of larval epithelium via programmed cell death and de novo formation of adult epithelium, with concurrent maturation of the muscles and connective tissue. Here, we will summarize our current understanding of the underlying molecular mechanisms, with a focus on more recent genetic and genome-wide studies.

Efficacy of nutritional selenium nanoparticles on growth performance, immune response, antioxidant capacity, expression of growth and immune-related genes, and post-stress recovery in juvenile Sobaity seabream (Sparidentex hasta)

This study evaluated the impacts of nano-Se on the growth, immunity, antioxidant capacity, physiological parameters, gene expression, and stress resistance of fingerling Sobaity seabream (Sparidentex hasta). The fish with an average weight of 21.5 ± 0.1 g were divided into four treatment groups in triplicates that received one of the test diets supplemented with varying levels of nano-Se: 0 (control), 0.5 (Se-0.5), 1 (Se-1), and 2 (Se-2) mg/Kg for 60 days. The results showed that final weight, weight gain rate, specific growth rate, feed intake, and feed conversion ratio improved with significant linear and quadratic trends (P < 0.05) in response to nano-Se-supplemented diets, and the best values were measured in the Se-2 group. Superoxide dismutase activity level remained unaffected among the four groups (P > 0.05). Catalase activity increased in nano-Se-supplemented groups, with the highest level measured in fish fed the Se-0.5 diet. Glutathione peroxidase activity levels were not significantly different between the control and nano-Se groups, but the lowest malondialdehyde concentration was detected in the Se-2 group. Nano-Se had no marked effect on total plasma Ig levels; however, the highest lysozyme activity and alternative complement activity (ACH50) were observed in the Se-0.5 and Se-2 groups, respectively. No significant differences (P > 0.05) were observed in plasma total protein, albumin, globulin, triglyceride, and thyroid hormone (T3 and T4) contents among the groups. However, the lowest cholesterol and low-density lipoprotein values and the highest high-density lipoprotein concentration were measured in the Se-2 group. The Se-0.5 and Se-1 groups exhibited significantly lower levels of aspartate aminotransferase activity, and the lowest alkaline phosphatase activity level was detected in the Se-1 group. The expression level of insulin-like growth factor I gene in all nano-Se-fed groups was significantly higher than the control. Also, the expression of interleukin-1β and lysozyme genes was significantly upregulated in nano-Se-supplemented groups, with the highest values in the Se-2 group. Following acute crowding stress, plasma cortisol and lactate levels at all post-stress time intervals were not significantly different among the experimental groups. Fish fed the Se-0.5 and Se-2 diets tended to have lower plasma glucose concentrations than other groups. In conclusion, dietary nano-Se at 2 mg/kg is recommended to promote growth performance and enhance antioxidant and immune parameters in Sobaity juveniles.

Associations of urinary non-persistent endocrine disrupting chemical biomarkers with early-to-mid pregnancy plasma sex-steroid and thyroid hormones

Background/ObjectivesPregnant women are exposed to numerous endocrine disrupting chemicals (EDCs) that can affect hormonal pathways regulating pregnancy outcomes and fetal development. Thus, we evaluated overall and fetal sex-specific associations of phthalate/replacement, paraben, and phenol biomarkers with sex-steroid and thyroid hormones. MethodsIllinois women (n = 302) provided plasma for progesterone, estradiol, testosterone, free T4 (FT4), total T4 (TT4), and thyroid stimulating hormone (TSH) at median 17 weeks gestation. Women also provided up-to-five first-morning urine samples monthly across pregnancy (8–40 weeks), which we pooled to measure 19 phthalate/replacement metabolites (reflecting ten parent compounds), three parabens, and six phenols. We used linear regression to evaluate overall and fetal sex-specific associations of biomarkers with hormones, as well as weighted quantile sum and Bayesian kernel machine regression (BKMR) to assess cumulative associations, non-linearities, and chemical interactions. ResultsIn women of relatively high socioeconomic status, several EDC biomarkers were associated with select hormones, without cumulative or non-linear associations with progesterone, FT4, or TT4. The biomarker mixture was negatively associated with estradiol (only at higher biomarker concentrations using BKMR), testosterone, and TSH, where each 10% mixture increase was associated with −5.65% (95% CI: −9.79, −1.28) lower testosterone and −0.09 μIU/mL (95% CI: −0.20, 0.00) lower TSH. Associations with progesterone, testosterone, and FT4 did not differ by fetal sex. However, in women carrying females, we identified an inverted u-shaped relationship of the mixture with estradiol. Additionally, in women carrying females, each 10% increase in the mixture was associated with 1.50% (95% CI: −0.15, 3.18) higher TT4, whereas in women carrying males, the mixture was associated with −1.77% (95% CI: −4.08, 0.58) lower TT4 and −0.18 μIU/mL (95% CI: −0.33, −0.03) lower TSH. We also identified select chemical interactions. ConclusionSome biomarkers were associated with early-to-mid pregnancy hormones. There were some sex-specific and non-linear associations. Future studies could consider how these findings relate to pregnancy/birth outcomes.

Fecal thyroid hormone metabolites in wild ungulates: a mini-review.

This review aims to analyse the fluctuations of fecal thyroid hormone metabolites (FTMs) related to environmental and individual variables in different species of wild ungulates and provide a collection of assay methods. The great advantage of fecal sampling is being completely non-invasive. A systemic search was conducted from 2019 to 2024, using data sources PubMed, Scopus, Web of Science, and the World Wide Web, and ten studies were found on this topic. Three studies used the radioimmunoassay method for FTMs analysis, while the others used a less expensive enzyme-linked immunosorbent assay. Most of these papers validated the method for the species-specific matrix. Related to the studied variables, some authors analysed FTM fluctuations only concerning individual variables, and others in response to both. Temperature and fecal cortisol metabolites (FCMs) were the most studied environmental and individual variables, respectively. Since FTMs are an integrative measure of plasma thyroid hormones, the information obtained from a non-invasive-assay method regarding wild ungulate physiology is becoming of great interest to the scientific community.

Association between low-normal thyroid function and advanced liver fibrosis in metabolic dysfunction-associated fatty liver disease patients: a retrospective cohort study.

Recent studies have found that thyroid function may be associated with the occurrence and development of advanced liver fibrosis in patients with metabolic dysfunction-associated fatty liver disease (MAFLD). However, the majority of such research has consisted of cross-sectional studies. This retrospective cohort study aimed to investigate the effect of low-normal thyroid function on advanced liver fibrosis in MAFLD patients over a 5-year period. This retrospective cohort study enrolled 825 outpatients and inpatients with MAFLD who attended the Third Affiliated Hospital of Sun Yat-sen University (Guangzhou, China) between January 2011 and December 2018. Based on plasma thyroid hormone and thyroid-stimulating hormone levels, these patients were divided into two groups, namely a low-normal thyroid function group and a strict-normal thyroid function group. The fibrosis-4 score was used to assess advanced liver fibrosis. A chi-square test was conducted to compare the occurrence of advanced fibrosis between the groups. Among the 825 MAFLD patients, 117 and 708 were defined as having low-normal thyroid function and strict-normal thyroid function, respectively. Follow-up data were available for 767 patients (93.0%) during a 5-year period. Eight (7.5%) MAFLD patients with low-normal thyroid function and 26 (3.9%) with strict-normal thyroid function developed advanced liver fibrosis and the cumulative incidence was not significantly different (P = 0.163). Stratification analysis showed that the lean MAFLD patients (body mass index ≤ 23 kg/m2) with low-normal thyroid function had a higher risk of advanced liver fibrosis than the lean MAFLD patients with strict-normal thyroid function (P < 0.05). Low-normal thyroid function is associated with advanced liver fibrosis among lean MAFLD patients.

Decreased hepatic thyroid hormone signaling in systemic and liver-specific but not brain-specific accelerated aging due to DNA repair deficiency in mice.

Thyroid hormone signaling is essential for development, metabolism, and response to stress but declines during aging, the cause of which is unknown. DNA damage accumulating with time is a main cause of aging, driving many age-related diseases. Previous studies in normal and premature aging mice, due to defective DNA repair, indicated reduced hepatic thyroid hormone signaling accompanied by decreased type 1 deiodinase (DIO1) and increased DIO3 activities. We investigated whether aging-related changes in deiodinase activity are driven by systemic signals or represent cell- or organ-autonomous changes. We quantified liver and plasma thyroid hormone concentrations, deiodinase activities and expression of T3-responsive genes in mice with a global, liver-specific and for comparison brain-specific inactivation of Xpg, one of the endonucleases critically involved in multiple DNA repair pathways. Both in global and liver-specific Xpg knockout mice, hepatic DIO1 activity was decreased. Interestingly, hepatic DIO3 activity was increased in global, but not in liver-specific Xpg mutants. Selective Xpg deficiency and premature aging in the brain did not affect liver or systemic thyroid signaling. Concomitant with DIO1 inhibition, Xpg -/- and Alb-Xpg mice displayed reduced thyroid hormone-related gene expression changes, correlating with markers of liver damage and cellular senescence. Our findings suggest that DIO1 activity during aging is predominantly modified in a tissue-autonomous manner driven by organ/cell-intrinsic accumulating DNA damage. The increase in hepatic DIO3 activity during aging largely depends on systemic signals, possibly reflecting the presence of circulating cells rather than activity in hepatocytes.

Towards translating in vitro measures of thyroid hormone system disruption to in vivo responses in the pregnant rat via a biologically based dose response (BBDR) model

Despite the number of in vitro assays that have been recently developed to identify chemicals that interfere with the hypothalamic-pituitary-thyroid axis (HPT), the translation of those in vitro results into in vivo responses (in vitro to in vivo extrapolation, IVIVE) has received limited attention from the modeling community. To help advance this field a steady state biologically based dose response (BBDR) model for the HPT axis was constructed for the pregnant rat on gestation day (GD) 20. The BBDR HPT axis model predicts plasma levels of thyroid stimulating hormone (TSH) and the thyroid hormones, thyroxine (T4) and triiodothyronine (T3). Thyroid hormones are important for normal growth and development of the fetus. Perchlorate, a potent inhibitor of thyroidal uptake of iodide by the sodium iodide symporter (NIS) protein, was used as a case study for the BBDR HPT axis model. The inhibitory blocking of the NIS by perchlorate was associated with dose-dependent steady state decreases in thyroid hormone production in the thyroid gland. The BBDR HPT axis model predictions for TSH, T3, and T4 plasma concentrations in pregnant Sprague Dawley (SD) rats were within 2-fold of observations for drinking water perchlorate exposures ranging from 10 to 30,000 μg/kg/d. In Long Evans (LE) pregnant rats, for both control and perchlorate drinking water exposures, ranging from 85 to 82,000 μg/kg/d, plasma thyroid hormone and TSH concentrations were predicted within 2 to 3.4- fold of observations. This BBDR HPT axis model provides a successful IVIVE template for thyroid hormone disruption in pregnant rats.

Using Recombinant Superoxide Dismutase to Control Oxidative Stress in the Gastrointestinal Tract of Cyclic Heat-Stressed Pigs.

Climate change is associated with an increased frequency and intensity of heat waves, posing a threat of heat stress to pig production. Heat stress compromises the efficiency of pig production partly due to causing oxidative stress, intestinal dysfunction, and inflammatory responses. Superoxide dismutase is an antioxidant enzyme reported to reduce oxidative stress and inflammation. Therefore, this experiment aimed to investigate whether recombinant superoxide dismutase (rSOD) could ameliorate oxidative stress and inflammatory responses in heat-stressed grower pigs. Sixty-four female pigs (Large White × Landrace, 27.8 ± 1.65 kg, mean ± SD) were randomly allocated to a control diet (standard grower feed, CON) or the control diet supplemented with 50 IU recombinant superoxide dismutase (rSOD) for 14 days. After acclimation to the diet, pigs were then housed under thermoneutral (TN, 20 °C, 35-50% relative humidity) or cyclic heat stress conditions (CHS, at 35 °C: 9 a.m. to 5 p.m. and 28 °C: 5 p.m. to 9 a.m., 35-50% relative humidity) for 3 days. Heat stress increased respiration rate (RR), skin and rectal temperature (RR and RT) (p < 0.001 for all), and reduced plasma thyroid hormone concentration (p < 0.001). The amount of oxidized glutathione (GSH:GSSG) was increased in the jejunum and ileum of CHS pigs. In the jejunum, rSOD also increased the amount of oxidized glutathione in both TN and CHS pigs, without any change in endogenous SOD activity. In the ileum, rSOD prevented increases in oxidized glutathione formation in the CHS pigs only. Taken together, this may reflect increased oxidative stress in both the jejunum and ileum in CHS pigs. Alternatively, rSOD increased the conversion of reduced to oxidized glutathione independently of CHS, possibly reflecting an increased overall SOD activity due to the addition of exogenous SOD. In conclusion, the use of in-feed SOD enzymes at a dose of 50 IU/kg may be a useful strategy for preventing oxidative stress in pigs.

Associations between prenatal exposure to polycyclic aromatic hydrocarbons and thyroid hormones in umbilical cord blood.

We explored the association between maternal urinary polycyclic aromatic hydrocarbon (PAH) metabolites and thyroid hormones in umbilical cord blood in 120 pairs of pregnant women and newborns. Maternal urinary PAH metabolites were measured using high-performance liquid chromatography with tandem mass spectrometry. Thyroid hormones were measured using a flow fluorescence assay. The dose-response relationship between PAH metabolites and thyroid hormones was analyzed using the generalized linear model and restricted cubic spline model. Results showed that ƩOH PAHs in maternal urine had a negative effect on triiodothyronine (T3). Associations between maternal urinary PAH metabolites and thyroid hormones in umbilical cord blood plasma were observed. Prenatal exposure to PAHs could affect neonatal thyroid hormones, thereby disrupting neonatal thyroid function.

A minimal human physiologically based kinetic model of thyroid hormones and chemical disruption of plasma thyroid hormone binding proteins.

The thyroid hormones (THs), thyroxine (T4) and triiodothyronine (T3), are under homeostatic control by the hypothalamic-pituitary-thyroid axis and plasma TH binding proteins (THBPs), including thyroxine-binding globulin (TBG), transthyretin (TTR), and albumin (ALB). THBPs buffer free THs against transient perturbations and distribute THs to tissues. TH binding to THBPs can be perturbed by structurally similar endocrine-disrupting chemicals (EDCs), yet their impact on circulating THs and health risks are unclear. In the present study, we constructed a human physiologically based kinetic (PBK) model of THs and explored the potential effects of THBP-binding EDCs. The model describes the production, distribution, and metabolism of T4 and T3 in the Body Blood, Thyroid, Liver, and Rest-of-Body (RB) compartments, with explicit consideration of the reversible binding between plasma THs and THBPs. Rigorously parameterized based on literature data, the model recapitulates key quantitative TH kinetic characteristics, including free, THBP-bound, and total T4 and T3 concentrations, TH productions, distributions, metabolisms, clearance, and half-lives. Moreover, the model produces several novel findings. (1) The blood-tissue TH exchanges are fast and nearly at equilibrium especially for T4, providing intrinsic robustness against local metabolic perturbations. (2) Tissue influx is limiting for transient tissue uptake of THs when THBPs are present. (3) Continuous exposure to THBP-binding EDCs does not alter the steady-state levels of THs, while intermittent daily exposure to rapidly metabolized TBG-binding EDCs can cause much greater disruptions to plasma and tissue THs. In summary, the PBK model provides novel insights into TH kinetics and the homeostatic roles of THBPs against thyroid disrupting chemicals.

Cell cycle activation in thyroid hormone-induced apoptosis and stem cell development during Xenopus intestinal metamorphosis.

Amphibian metamorphosis resembles mammalian postembryonic development, a period around birth when many organs mature into their adult forms and when plasma thyroid hormone (T3) concentration peaks. T3 plays a causative role for amphibian metamorphosis. This and its independence from maternal influence make metamorphosis of amphibians, particularly anurans such as pseudo-tetraploid Xenopus laevis and its highly related diploid species Xenopus tropicalis, an excellent model to investigate how T3 regulates adult organ development. Studies on intestinal remodeling, a process that involves degeneration of larval epithelium via apoptosis and de novo formation of adult stem cells followed by their proliferation and differentiation to form the adult epithelium, have revealed important molecular insights on T3 regulation of cell fate during development. Here, we review some evidence suggesting that T3-induced activation of cell cycle program is important for T3-induced larval epithelial cell death and de novo formation of adult intestinal stem cells.