Increased Epoxyeicosatrienoic Acids and Hydroxyeicosatetraenoic Acids After Treatment of Iodide Intake Adjustment and 1,25-Dihydroxy-Vitamin D Supplementation in High Iodide Intake-Induced Hypothyroid Offspring Rats.

This study aimed to investigate the potential role of fatty acids in high iodide intake-induced hypothyroidism and its complications and also in the intervention of iodide intake adjustment and 1,25-dihydroxy-vitamin D [1,25(OH)D] supplementation. Pregnant rats were allocated to two groups, namely, normal iodide (NI, 7.5 μg/day) intake and 100 times higher-than-normal iodide (100 HI, 750 μg/day) intake. The offspring were continuously administered potassium iodide from weaning [i.e., postnatal day 21 (PN21)] to PN90. After PN90, the offspring were either administered iodide intake adjustment (7.5 μg/day) or 1,25(OH)D supplementation (5 μg·kg·day), or both, for 4 weeks. Thyroid function tests (free triiodothyronine, free thyroxine, thyrotropin, thyroid peroxidase antibody, and thyroglobulin antibody), blood lipids (triglyceride, total cholesterol, free fatty acid, and low-density lipoprotein cholesterol), and vitamin D3 (VD3) levels were detected by ELISA. Cardiac function was measured by echocardiography. Blood pressure was measured using a non-invasive tail-cuff system. The serum fatty acids profile was analyzed by liquid chromatography-mass spectrometry. In the offspring rats with continued 100 HI administration, the levels of 8,9-dihydroxyeicosatrienoic acid (8,9-DHET) and thromboxane B2 (TXB2) were decreased, while those of prostaglandin J2 (PGJ2), prostaglandin B2 (PGB2), 4-hydroxydocosahexaenoic acid (4-HDoHE), 7-HDoHE, 8-HDoHE, and 20-HDoHE were increased. Significant correlations were found between PGB2, 8,9-DHET, 7-HDoHE levels and thyroid dysfunction, between PGJ2, 20-HDoHE, PGB2, 8,9-DHET levels and cardiac dysfunction, between PGJ2, 20-HDoHE levels and hypertension, between 4-HDoHE, 8-HDoHE, TXB2 levels and dyslipidemia, and between PGB2 and decreased VD3 level. After the treatment of iodide intake adjustment and 1,25(OH)D supplementation, the levels of 16-hydroxyeicosatetraenoic acids (16-HETE), 18-HETE, 5,6-epoxyeicosatrienoic acid (5,6-EET), 8,9-EET, 11,12-EET, 14,15-EET, PGE2, 5-oxo-ETE, and 15-oxo-ETE were increased. The significant associations between PGE2, 16-HETE, 18-HETE and improved thyroid function and also between 5,6-EET, 11,12-EET, 14,15-EET, 16-HETE, 15-oxo-ETE and attenuated dyslipidemia were detected. Increased levels of prostaglandins (PGs) and HDoHEs and decreased levels of 8,9-DHET and TXB2 might occur in the progression of cardiac dysfunction, hypertension, and dyslipidemia in high iodide intake-induced hypothyroidism. The increased levels of EETs and HETEs might help to ameliorate these complications after iodide intake adjustment and 1,25(OH)D supplementation.