Szczuko Małgorzata, Kwiatkowska Lidia, Szczuko Urszula, Rudak Leon, Ryterska Karina, Syrenicz Anhelli, Pobłocki Jakub, Drozd Arleta
Department of Human Nutrition and Metabolomics, Pomeranian Medical University in Szczecin, 71-460 Szczecin, Poland.
Department of Bromatology and Nutritional Diagnostics, Pomeranian Medical University in Szczecin, 71-460 Szczecin, Poland.
Int J Mol Sci. 2025 Jul 6;26(13):6507. doi: 10.3390/ijms26136507.
The incidence of Hashimoto's disease (HD) increases with age and in people who have other autoimmune diseases. It is characterized by lymphocytic infiltration, fibrosis, and atrophy of the thyroid parenchyma with the simultaneous presence of thyroid peroxidase antibodies (ATPO) and/or thyroglobulin antibodies (ATG). Eicosanoids are formed via the cyclooxygenase (COX), lipoxygenase (LOX), and monooxygenase (CYP450) pathways with arachidonic acid (ARA), resulting in the production of epoxyeicosatrienoic acids (EETs) or hydroxyeicosatetraenoic acids (HETEs). These eicosanoids can act in an autocrine or paracrine manner on target cells. This study aimed to examine whether a gluten-free diet (GFD) can modulate the enzymatic pathways of the pro-inflammatory ARA cascade. The study material consisted of serum samples from Caucasian female patients with HD aged 18-55 years. Participants were enrolled in the study based on the presence of an ultrasound characteristic of HD, and elevated serum levels of anti-thyroid peroxidase antibodies and anti-thyroglobulin antibodies. Patients with confirmed celiac disease did not participate in the study. A total of 78 samples were analyzed, with 39 collected after 3 months of following a GFD. Eicosanoids (thromboxane B2, prostaglandin E2, leukotriene B4, and 16R-hydroxy-5Z,8Z,11Z,14Z-eicosatetraenoic acid (16-RS HETE)) were extracted using high-performance liquid chromatography. The contribution of leukotriene (LTB) was analyzed in the LOX pathway, prostaglandins (PGE2) and thromboxane (TXB2) were selected for the involvement of the COX pathway, and 16RS HETE was used for the CYP450 pathway. All parameters were analyzed before and after a 3-month dietary intervention that included a gluten-free diet. In the obtained results, only one mediator, leukotriene B4, was significant ( < 0.05). The mean level on the initial visit was 0.202 ± 0.11 (SD), while it was 0.421 ± 0.27 (SD) on the subsequent visit, indicating a significant increase in its level after implementing a GFD. Although there was a trend in the CYP 450 pathway of decreased 16-RS HETE, the presented correlations show that thromboxane B4 and 16RS-HETE were positively correlated with the body mass and body fat mass of the examined patients. There was a trend in the CYP 450 pathway of decreased 16-RS HETE after GFD. Thromboxane B4 and 16RS-HETE levels before GFD were positively correlated with the body mass and body fat mass of the examined patients. A gluten-free diet in HD does not suppress the synthetic pathways of LOX, COX, or cytochrome P450 (CYP450). The level of adipose tissue has a greater impact on the inflammatory processes in HD than a gluten-free diet. This study does not confirm the suppressive effect of a gluten-free diet on the pro-inflammatory arachidonic acid cascade in any of the three analyzed mediator synthesis LOX, COX, CYP450 pathways.
桥本氏病（HD）的发病率随年龄增长以及在患有其他自身免疫性疾病的人群中升高。其特征为淋巴细胞浸润、纤维化以及甲状腺实质萎缩，同时存在甲状腺过氧化物酶抗体（ATPO）和/或甲状腺球蛋白抗体（ATG）。类花生酸通过环氧化酶（COX）、脂氧合酶（LOX）和单加氧酶（CYP450）途径与花生四烯酸（ARA）形成，导致环氧二十碳三烯酸（EETs）或羟基二十碳四烯酸（HETEs）的产生。这些类花生酸可通过自分泌或旁分泌方式作用于靶细胞。本研究旨在探讨无麸质饮食（GFD）是否能调节促炎性ARA级联反应的酶促途径。研究材料包括18 - 55岁患有HD的白种女性患者的血清样本。参与者基于HD的超声特征以及血清抗甲状腺过氧化物酶抗体和抗甲状腺球蛋白抗体水平升高而被纳入研究。确诊为乳糜泻的患者未参与研究。共分析了78个样本，其中39个是在遵循GFD 3个月后采集的。使用高效液相色谱法提取类花生酸（血栓素B2、前列腺素E2、白三烯B4和16R - 羟基 - 5Z,8Z,11Z,14Z - 二十碳四烯酸（16 - RS HETE））。在LOX途径中分析白三烯（LTB）的贡献，选择前列腺素（PGE2）和血栓素（TXB2）用于COX途径的参与情况，16RS HETE用于CYP450途径。在包括无麸质饮食的3个月饮食干预前后分析所有参数。在所得结果中，只有一种介质白三烯B4具有显著性（<0.05）。初次就诊时的平均水平为0.202±0.11（标准差），而后续就诊时为0.421±0.27（标准差），表明实施GFD后其水平显著升高。尽管在CYP 450途径中16 - RS HETE有降低的趋势，但所呈现的相关性表明血栓素B4和16RS - HETE与所检查患者的体重和体脂量呈正相关。GFD后CYP 450途径中16 - RS HETE有降低的趋势。GFD前血栓素B4和16RS - HETE水平与所检查患者的体重和体脂量呈正相关。HD患者的无麸质饮食不会抑制LOX、COX或细胞色素P450（CYP450）的合成途径。脂肪组织水平对HD炎症过程的影响大于无麸质饮食。本研究未证实在所分析的三种介质合成LOX、COX、CYP450途径中的任何一种中，无麸质饮食对促炎性花生四烯酸级联反应有抑制作用。
