Details

Autor(en) / Beteiligte

• Chen, Yuying
• Zhou, Chengcong
• Bian, Yishan
• Fu, Fangda
• Zhu, Bian'an
• Zhao, Xuyan
• Zhang, Muxin
• Zhou, Chunyuan
• Yao, Sai
• Zhang, Zhiguo
• Luo, Huan
• Ge, Yuying
• Wu, Chengliang
• Ruan, Hongfeng

Titel

Cadmium exposure promotes thyroid pyroptosis and endocrine dysfunction by inhibiting Nrf2/Keap1 signaling

Ist Teil von

• Ecotoxicology and environmental safety, 2023-01, Vol.249, p.114376, Article 114376

Ort / Verlag

Netherlands: Elsevier Inc

Erscheinungsjahr

2023

Quelle

MEDLINE

Beschreibungen/Notizen

• Cadmium (Cd) is a ubiquitous toxic metal and environmental pollutant. Increasing studies have shown that Cd exposure increases the incidence of various endocrine system diseases, including thyrotoxicity reflected by thyroid structural damage and endocrine toxicity. However, the observed outcomes are complex and conflicting, leading to the mechanism of Cd-induced thyrotoxicity remaining obscure. In this study, 4-week-old male C57BL/6 mice were given 2 or 7 mg/kg Cadmium Chloride (CdCl2) intragastrically for 4 and 8 weeks, and the Cd-mediated thyrotoxicity was evaluated by determining alterations in thyroid structure and endocrine function, and alterations of oxidant stress, apoptosis, and pyroptosis. Our data showed that Cd exposure could reduce body weight and induce thyrotoxicity by impairing thyroid follicular morphology and endocrine function, accompanied by elevated oxidative stress and apoptosis, macrophage infiltration, and inflammatory cytokine secretion. Importantly, Cd significantly promoted thyroid follicular cell pyroptosis by increasing Nlrp3, Asc, Caspase-1, Gsdmd, IL-1β, and IL-18 expression. Mechanistical analysis suggested that Cd treatment could inhibit antioxidant pathway by downregulating antioxidant response protein, Nrf2, and upregulating its negative feedback regulator, Keap1. Collectively, our in vivo findings suggest that Cd exposure could facilitate thyroid follicular cell pyroptosis by inhibiting Nrf2/Keap1 signaling, thereby disrupting thyroid tissue structure and endocrine function, which offers novel insights into the Cd-mediated detrimental consequences on thyroid homeostasis. •Cd exposure reduces body weight, disrupts thyroid structure and hormone homeostasis.•Cd exposure facilitates apoptosis of thyroid and inflammatory response in thyroid.•Cd augments pyroptosis of thyroid follicular cell by suppressing Nrf2/Keap1 pathway.