Cardiac ischemia/reperfusion injury is inversely affected by thyroid hormones excess or deficiency in male Wistar rats.

AIM: Thyroid dysfunctions can increase the risk of myocardial ischemia and infarction. However, the repercussions on cardiac ischemia/reperfusion (IR) injury remain unclear so far. We report here the effects of hypothyroidism and thyrotoxicosis in the susceptibility to IR injury in isolated rat hearts compared to euthyroid condition and the potential role of antioxidant enzymes. METHODS: Hypothyroidism and thyrotoxicosis were induced by administration of methimazole (MMZ, 300 mg/L) and thyroxine (T4, 12 mg/L), respectively in drinking water for 35 days. Isolated hearts were submitted to IR and evaluated for mechanical dysfunctions and infarct size. Superoxide dismutase types 1 and 2 (SOD1 and SOD2), glutathione peroxidase types 1 and 3 (GPX 1 and GPX3) and catalase mRNA levels were assessed by quantitative RT-PCR to investigate the potential role of antioxidant enzymes. RESULTS: Thyrotoxicosis elicited cardiac hypertrophy and increased baseline mechanical performance, including increased left ventricle (LV) systolic pressure, LV developed pressure and derivatives of pressure (dP/dt), whereas in hypothyroid hearts exhibited decreased dP/dt. Post-ischemic recovery of LV end-diastolic pressure (LVEDP), LVDP and dP/dt was impaired in thyrotoxic rat hearts, whereas hypothyroid hearts exhibited improved LVEDP and decreased infarct size. Catalase expression was decreased by thyrotoxicosis. CONCLUSION: Thyrotoxicosis was correlated, at least in part, to cardiac remodeling and increased susceptibility to IR injury possibly due to down-regulation of antioxidant enzymes, whereas hypothyroid hearts were less vulnerable to IR injury.

Social stress-induced hypothyroidism is attenuated by antidepressant treatment in rats.

Although serotonergic system has been classically implicated in mood modulation, there has been relatively little study on the relationship between this system and thyroid hormones (TH) economy in stress models. When TH are studied, the effects of stress on thyroid function seems to be complex and depend on the kind and time of stress which counts for the elusiveness of mechanisms underlying changes in TH economy. Herein, we hypothesized that serum TH are affected in a time-dependent fashion after repeated social stressful stimuli and serotonergic system is implicated in these changes. Therefore, we aimed to investigate the possible alterations in thyroid hormone economy and type 1 (D1) and type 2 (D2) deiodinase activity in a model of social defeat stress. Thereafter, we tested the responsiveness of these changes to fluoxetine treatment. Both short (STS) and a long-term (LTS) stress were performed. Blood samples were drawn just before and 1 (STS) or 4 and 8 weeks (LTS) after the beginning of stress to assess serum T4, T3 and corticosterone. Deiodinases activity was assessed at the end of each protocol. Stress-induced behavior studied in open field arena and hypercorticosteronemia were mainly observed in LTS (week 4). Stress-induced behavior was associated to hypothyroidism which occurred before, since week 1 in stressed group. Serum TH was restored to control levels in week 8, when behavior changes were not observed anymore, and was mainly associated with high brown adipose tissue D2 activity since thyroid and liver D1 activity were low or normal in the STS and LTS respectively in stressed rats compared to control. Antidepressant study revealed that fluoxetine treatment (10mg/kg po during four weeks) fully reversed stress-induced behavior and normalized serum T4, but not T3 levels and hypercorticosteronemia in stressed group compared to control. The current work adds new concepts concerning TH metabolism changes induced by social stress and suggests that serotonergic system impairment may take part in the key events which ultimately lead to hypothyroxinemia and behavioral changes induced by chronic social defeat. This article is part of a Special Issue entitled 'Anxiety and Depression'.