Thyroxine replacement modifies changes in deiodinase and thyroid hormone transporter expression induced by subclinical hypothyroidism in rats.

PURPOSE: The potential benefits of treating subclinical hypothyroidism (SCH) are unclear and still controversial. Thus, we surgically induced SCH in rats and evaluated the effects of thyroxine (T4) replacement on the gene expression levels of deiodinases and thyroid hormone (TH) transporters in different tissues. METHODS: SCH was induced by hemithyroid electrocauterization. The control animals underwent the same surgical procedure but were not subjected to electrocauterization (sham). After 14 days, half of the SCH animals were treated with T4 (SCH + T4). At the end of the experimental protocol, all of the rats were euthanized, serum hormone concentrations were measured, and RNA analyses were performed on different tissues and organs. RESULTS: Consistent with previous studies, we observed increased TSH levels, normal TH levels, and reduced hypothalamic TRH expression in the SCH group. Additionally, Dio2 mRNA expression was downregulated in the hippocampus and pituitary, and Dio1 was upregulated in the kidney and pituitary of the SCH animals. The changes in Dio3 expression were tissue-specific. Concerning TH transporters, Mct10 expression was upregulated in the pituitary, kidney, hypothalamus, and hippocampus, and Mct8 expression was downregulated in the kidney of the SCH group. Crym expression was upregulated in the kidney and pituitary. Notably, T4 replacement significantly attenuated serum TSH levels and reverted Dio1, Dio2, Mct10, and Crym expression in the pituitary, hippocampus, and kidney to levels that were similar to the sham group. Tissue-specific responses were also observed in the liver and hypothalamus. CONCLUSION: Our results indicate that treatment of SCH should be considered before the appearance of clinical symptoms of hypothyroidism.

Topical and systemic use of Joannesia princeps vell. LC seed oil in acute pain and inflammation induced by different agents.

ETHNOPHARMACOLOGICAL RELEVANCE: Joannesia princeps (SOJP) has been used in folk medicine as anthelmintic treatment and cutaneous wound healing. AIM OF THE STUDY: The purpose of this study is to evaluate the pharmacological activity of seed oil of Joannesia princeps, administered systemically and topically, on acute pain and inflammation. MATERIALS AND METHODS: Male swiss mice were treated orally and topically with seed oil of Joannesia princeps in models of acute pain (acetic acid-induced abdominal writhing, formalin-induced licking behaviour and tail flick tests) and acute inflammation (carrageenan- and histamine-induced paw oedema; arachidonic acid-, capsaicin- and croton oil-induced ear oedema and air pouch tests), besides the open field model in the motor performance evaluation. RESULTS: Seed oil of Joannesia princeps showed systemic action against acute pain in abdominal writhing test (37% and 56% inhibition in the number of writhes at doses of 30 and 100 mg/kg, respectively) and in the second phase of formalin-induced licking behaviour test (29%, 47 and 52% inhibition in the licking time at doses of 10, 30 and 100 mg/kg, respectively), as well as reducing croton oil-induced ear oedema by 72%, leukocyte recruitment and production of TNF-α and IL-6 in the air pouch tests. In addition, topical administration of SOJP inhibited carrageenan-induced paw oedema by 39% at dose of 500 µg/paw and inhibited histamine-induced oedema by 43 and 52% at doses of 300 and 500 µg/paw, respectively. SOJP also decreased croton oil-induced ear oedema by 67% at dose of 500 µg/paw and arachidonic acid-induced ear oedema by 63% at dose of 500 µg/paw, reducing the production of TNF-α, IL-1ß and MIP2 in both. In addition, no adverse effects were observed at doses up to 2000 mg/kg. CONCLUSIONS: Seed oil of Joannesia princeps presents antinociceptive and anti-inflammatory actions through its topical and systemic administration, promoted by inhibition of leukocyte recruitment and cytokine production (TNF-α, IL-1ß, IL-6 and MIP-2).

Selenium supplementation during pregnancy and lactation promotes metabolic changes in Wistar rats' offspring.

Epidemiological and animal studies have demonstrated a strong association between selenium (Se) supplementation and metabolic disorders, we aimed to evaluate whether maternal Se supplementation was able to change metabolic parameters in rats' offspring. Moreover, as Se is a deiodinase (DIO) cofactor, we decided to investigate how thyroid hormones (THs) would be involved in such metabolic changes. Thereby, two groups (n = 6, ~250 g) of female Wistar rats underwent isotonic saline or sodium selenite (1 mg/kg, p.o.) treatments. Although there were no significant differences in body weight between groups, the Se treatment during pregnancy and lactation increased milk intake and the visceral white adipose tissue (WAT) in offspring. The rats whose mothers were treated with Se also presented an improvement in the glucose tolerance test and in the glucose-stimulated insulin secretion. Regarding the lipid metabolism, the Se group had a reduction of triglycerides in the liver and in WAT. These metabolic changes were accompanied by an increase in serum triiodothyronine (T3 ) and in DIO 2 expression in brown adipose tissue (BAT). We further demonstrate an increased expression of peroxisome proliferator-activated receptor-gamma coactivator 1-alpha (PGC-1α) and nuclear respiratory factor-1 (NRF-1) mRNA in the liver. In adulthood offspring, Se supplementation programs thyroid function, glucose homeostasis, and feeding behaviour. Taken together, there is no indication that Se programming causes insulin resistance. Moreover, we conjecture that these metabolic responses are induced by increased thyroxine (T4 ) to T3 conversion by DIO2 in BAT and mediated by altered transcription factors expression associated with oxidative metabolism control in the liver.

Sodium selenite supplementation during pregnancy and lactation promotes anxiolysis and improves mnemonic performance in wistar rats' offspring.

Selenium is a micronutrient which is part of selenoprotein molecules and participates in a vast number of physiological roles and, among them,we have fetal and neonatal development. Therefore, the aimof this studywas to evaluate possible behavioral changes in offspring of female rats supplemented during pregnancy and lactation with sodium selenite. To address that, we treated two groups of female rats by saline or sodium selenite at a dose of 1mg/kg through oral route and performed neurochemical and behavioral tests. In the offspring, the thyroid profile and hippocampal neurochemistrywere evaluated. Behavioral testswere performed in pups both during childhood and adulthood. We found out that selenium (Se) supplementation increased serum levels of triiodothyronine (25%, p b 0.001) and thyroxine (18%, p b 0.05) and promoted a tryptophan hydroxylase 2 (TPH 2) expression decrease (17%, p b 0.01) and tyrosine hydroxylase (TH) expression increase (202%, p b 0.01) in the hippocampus. The cholinesterase activity was decreased (28%, p b 0.01) in Se supplemented rats, suggesting a neurochemical modulation in the hippocampal activity. During childhood, the Sesupplemented offspring had a reduction in anxiety-like behavior both in elevated plus maze test and in light­dark box test. In adulthood, Se-treated pups had an increase in the locomotor activity (36%, p b 0.05) and in rearing episodes (77%, p b 0.001) in the open field test, while in the elevated plus maze test they also exhibited an increase in the time spent in the open arms (243%, p b 0.01). For the object recognition test, Se-treated offspring showed increase in the absolute (230.16%, p b 0.05) and relative index discrimination (234%, p b 0.05). These results demonstrate that maternal supplementation by sodium selenite promoted psychobiological changes both during childhood and adulthood. Therefore, the behavioral profile observed possibly can be explained by neurochemical changes induced by thyroid hormones during the critical period of the central nervous system ontogeny.