Sesamin alleviated fluoride – induced thyroid endocrine disruption in zebrafish (Danio rerio).

Fluorine, a highly reactive halogen element, is widely distributed in nature as inorganic or organic fluoride compounds (Barbier et al., 2010). Fluoride plays an essential role in the growth and development of humans and animals (Chen et al., 2013). Fluoride has a double threshold effects, moderate intake of fluoride can promote the growth and development of the body and maintain the normal structure and physiological function of bones and teeth. However, excessive intake of fluoride can cause dental fluorosis and skeletal fluorosis, and produce toxic effects on many tissues and organs. (Srivastava et al., 2020). Evidence showed that brushing a child’s teeth with toothpaste containing higher fluoride levels (1000 parts per million (ppm) or more) in toothpaste is associated with an increased risk of fluorosis (Wong et al., 2010). Natural and anthropogenic activities are two primary sources of fluoride, such as volcano eruptions, rock weathering, and fluoride-containing industrial discharge, which easily enter the aquatic ecosystem (Daiwile et al., 2019). The fluoride concentration in unpolluted freshwater is usually from 0.01 to 0.3 mg/L, while it reaches from 10 to 79.2 mg/L in groundwater in many fluorosis areas (Yadav et al., 2019). Excessive fluoride in water has a direct and severe impact on aquatic organisms, including abnormal behavior, growth inhibition, damage to reproductive and immune function, and endocrine disorders (Chen et al., 2016; Cao et al., 2020; Li et al., 2020; Zhang et al., 2022).

Thyroid hormones (THs) have key role in maintaining physiological conditions, such as brain development, metabolism, energy balance, and growth (Meeker and Ferguson, 2011). Impaired thyroid signaling is associated with harmful effects, such as neuro-developmental defects, metabolism derangement, and immune dysregulation (Brent, 2012). A previous study has shown that the thyroid gland is one of the most sensitive organs to fluoride (Liu et al., 2002). Research on fluorosis has shown that the thyroid endocrine function changes dynamically as fluoride exposure time and dose increase. Previous studies have shown that high fluoride can disturb thyroid endocrine function, and the toxic effect gradually increases with the increase in fluoride exposure time and dose (Chen et al., 2016). However, there is no effective alleviating strategy for the toxic effects of fluoride on thyroid.

Sesamin, the liposoluble and furfural lignan rich in sesamum seeds and oil, has a wide range of physiological functions, such as antioxidant (Cao et al., 2015, 2020), antiapoptosis (Deng et al., 2013), anticancer (Kuo et al., 2020), neuroprotection (Ruankham et al., 2021), liver protection (Cao et al., 2020), and endocrine regulation (Zhao et al., 2017). At the same time, the effect of sesamin as a feed additive on the nutritional quality of muscle as human food in terms and fish welfare in aquaculture has been widely studied (Trattner et al., 2011). Our studies have shown that sesamin can protect the kidney against fluoride-induced apoptosis by regulating the JNK signaling pathway in carp and can attenuate histological alterations, oxidative stress, and expression of immune-related genes in the liver of zebrafish exposed to fluoride (Cao et al., 2015, 2020). However, it’s protective effects and molecular mechanisms on thyroid endocrine dysfunction caused by fluoride are still unclear.

The genomes of zebrafish (Danio rerio) and humans are highly related and contain orthologous genes encoding enzymes and regulatory molecules that control similar aspects of development and body homeostasis (Horzmann and Freeman, 2018). In addition, the mechanisms of zebrafish thyroid development are generally comparable to humans (Bambino and Chu, 2017). Our previous research has shown that fluoride can lead to thyroid endocrine dysfunction in zebrafish. In particular, male zebrafish are more sensitive to fluoride (Baksi and Pradhan, 2021; Chen et al., 2016; Lima et al., 2006). At the same time, sesamin has an improved effect on multi-symptom caused by fluorosis. However, there is no report on whether sesamin can alleviate thyroid endocrine disorders in fluoride-exposed zebrafish. Thus, in this study, zebrafish were selected to explore the protective effects and underlying mechanism of sesamin on fluoride-induced thyroid endocrine disruption by observing the growth and development, thyroid morphology, determining THs content and oxidative stress level, and measuring the expression levels of endocrine-related mRNA. This can provide adequate data support for alleviating fluoride-toxic effects and evaluating the potency of sesamin on endocrine regulation.