E Sahin1, E Bektur1, C Baycu2, D Burukoglu Dönmez1, B Kaygısız3. 1. Eskisehir Osmangazi University, Medicine School, Department of Histology and Embryology, Eskisehir, Turkey. 2. Okan University, Medicine School, Department of Histology and Embryology, Istanbul, Turkey. 3. Eskisehir Osmangazi University, Medicine School, Department of Pharmacology, Eskisehir, Turkey.
Abstract
PURPOSE: In this study, we aimed to investigate the relationship between hypothyroidism and sterile inflammation in rat heart tissue. METHODS: Groups; control group (fed with standard rat chow diet and tab water) and the hypothyroid group (fed with a standard rat chow diet and tap water containing 0.05% 6-n-propyl-2-thiouracil for 6-weeks). At the end of the experiment, histopathologic examination was performed. The T3, T4, TSH and myocardial malondialdehyde (MDA) measurements were performed with an ELISA kit. TUNEL assay was performed to demonstrate apoptosis. Sterile inflammation markers, caspase-1 and NLRP3, were investigated by immunohistochemistry and western blot. RESULTS: In histopathological examination, we observed leukocyte infiltration, myocardial atrophy, pyknotic nucleated cells and cytoplasmic vacuolization in hypothyroid group whereas the control group showed normal structure. MDA levels in myocardial tissue were significantly high in hypothyroid group when compared to the control group (P<0.05). Myocardial apoptosis increased in hypothyroid group when compared to the control group. NLRP3 and caspase-1 immunoreactivity was higher in the hypothyroid group. In ELISA results, we found significantly higher level of TSH and lower levels of T3 and T4 in hypothyroid group when compared to the control group. CONCLUSION: Hypothyroidism increased oxidative stress, and caused inflammatory alterations in cardiac tissue. In addition, our study also suggested that thyroid hormone deficiency would increase the amounts of cardiac NLRP3 and caspase-1 protein, which indicates that hypothyroidism exerts its destructive effects through sterile inflammation. Elucidation of sterile inflammation-associated pathways may produce promising results in the treatment of hypothyroidism-induced cardiac damage.
PURPOSE: In this study, we aimed to investigate the relationship between hypothyroidism and sterile inflammation in rat heart tissue. METHODS: Groups; control group (fed with standard rat chow diet and tab water) and the hypothyroid group (fed with a standard rat chow diet and tap water containing 0.05% 6-n-propyl-2-thiouracil for 6-weeks). At the end of the experiment, histopathologic examination was performed. The T3, T4, TSH and myocardial malondialdehyde (MDA) measurements were performed with an ELISA kit. TUNEL assay was performed to demonstrate apoptosis. Sterile inflammation markers, caspase-1 and NLRP3, were investigated by immunohistochemistry and western blot. RESULTS: In histopathological examination, we observed leukocyte infiltration, myocardial atrophy, pyknotic nucleated cells and cytoplasmic vacuolization in hypothyroid group whereas the control group showed normal structure. MDA levels in myocardial tissue were significantly high in hypothyroid group when compared to the control group (P<0.05). Myocardial apoptosis increased in hypothyroid group when compared to the control group. NLRP3 and caspase-1 immunoreactivity was higher in the hypothyroid group. In ELISA results, we found significantly higher level of TSH and lower levels of T3 and T4 in hypothyroid group when compared to the control group. CONCLUSION: Hypothyroidism increased oxidative stress, and caused inflammatory alterations in cardiac tissue. In addition, our study also suggested that thyroid hormone deficiency would increase the amounts of cardiac NLRP3 and caspase-1 protein, which indicates that hypothyroidism exerts its destructive effects through sterile inflammation. Elucidation of sterile inflammation-associated pathways may produce promising results in the treatment of hypothyroidism-induced cardiac damage.
Authors: Chun-Jen Chen; Hajime Kono; Douglas Golenbock; George Reed; Shizuo Akira; Kenneth L Rock Journal: Nat Med Date: 2007-06-17 Impact factor: 53.440
Authors: Shankar S Iyer; Wilco P Pulskens; Jeffrey J Sadler; Loes M Butter; Gwendoline J Teske; Tyler K Ulland; Stephanie C Eisenbarth; Sandrine Florquin; Richard A Flavell; Jaklien C Leemans; Fayyaz S Sutterwala Journal: Proc Natl Acad Sci U S A Date: 2009-11-16 Impact factor: 11.205