Cadmium exposure promotes thyroid pyroptosis and endocrine dysfunction by inhibiting Nrf2/Keap1 signaling
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...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-01-01
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| Series: | Ecotoxicology and Environmental Safety |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651322012167 |
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| author | Yuying Chen Chengcong Zhou Yishan Bian Fangda Fu Bian'an Zhu Xuyan Zhao Muxin Zhang Chunyuan Zhou Sai Yao Zhiguo Zhang Huan Luo Yuying Ge Chengliang Wu Hongfeng Ruan |
| author_facet | Yuying Chen Chengcong Zhou Yishan Bian Fangda Fu Bian'an Zhu Xuyan Zhao Muxin Zhang Chunyuan Zhou Sai Yao Zhiguo Zhang Huan Luo Yuying Ge Chengliang Wu Hongfeng Ruan |
| author_sort | Yuying Chen |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-11T00:56:20Z |
| format | Article |
| id | doaj.art-36b6e79193dd47619b842c8acf724da1 |
| institution | Directory Open Access Journal |
| issn | 0147-6513 |
| language | English |
| last_indexed | 2024-04-11T00:56:20Z |
| publishDate | 2023-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ecotoxicology and Environmental Safety |
| spelling | doaj.art-36b6e79193dd47619b842c8acf724da12023-01-05T04:30:26ZengElsevierEcotoxicology and Environmental Safety0147-65132023-01-01249114376Cadmium exposure promotes thyroid pyroptosis and endocrine dysfunction by inhibiting Nrf2/Keap1 signalingYuying Chen0Chengcong Zhou1Yishan Bian2Fangda Fu3Bian'an Zhu4Xuyan Zhao5Muxin Zhang6Chunyuan Zhou7Sai Yao8Zhiguo Zhang9Huan Luo10Yuying Ge11Chengliang Wu12Hongfeng Ruan13Institute of Orthopaedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Zhejiang Provincial Hospital of Chinese Medicine, Hangzhou 310053, China; The Fourth Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou 310053, ChinaInstitute of Orthopaedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Zhejiang Provincial Hospital of Chinese Medicine, Hangzhou 310053, ChinaInstitute of Orthopaedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Zhejiang Provincial Hospital of Chinese Medicine, Hangzhou 310053, ChinaInstitute of Orthopaedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Zhejiang Provincial Hospital of Chinese Medicine, Hangzhou 310053, ChinaThe Fourth Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou 310053, ChinaThe Fourth Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou 310053, ChinaInstitute of Orthopaedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Zhejiang Provincial Hospital of Chinese Medicine, Hangzhou 310053, ChinaInstitute of Orthopaedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Zhejiang Provincial Hospital of Chinese Medicine, Hangzhou 310053, ChinaInstitute of Orthopaedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Zhejiang Provincial Hospital of Chinese Medicine, Hangzhou 310053, ChinaInstitute of Orthopaedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Zhejiang Provincial Hospital of Chinese Medicine, Hangzhou 310053, ChinaDepartment of Pharmacy, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China; Corresponding author.Institute of Orthopaedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Zhejiang Provincial Hospital of Chinese Medicine, Hangzhou 310053, ChinaInstitute of Orthopaedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Zhejiang Provincial Hospital of Chinese Medicine, Hangzhou 310053, ChinaInstitute of Orthopaedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Zhejiang Provincial Hospital of Chinese Medicine, Hangzhou 310053, China; Correspondence to: Institute of Orthopaedics and Traumatology, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310053, China.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.http://www.sciencedirect.com/science/article/pii/S0147651322012167CadmiumThyroidEndocrine dysfunctionPyroptosisNrf2/Keap1 signaling |
| spellingShingle | Yuying Chen Chengcong Zhou Yishan Bian Fangda Fu Bian'an Zhu Xuyan Zhao Muxin Zhang Chunyuan Zhou Sai Yao Zhiguo Zhang Huan Luo Yuying Ge Chengliang Wu Hongfeng Ruan Cadmium exposure promotes thyroid pyroptosis and endocrine dysfunction by inhibiting Nrf2/Keap1 signaling Ecotoxicology and Environmental Safety Cadmium Thyroid Endocrine dysfunction Pyroptosis Nrf2/Keap1 signaling |
| title | Cadmium exposure promotes thyroid pyroptosis and endocrine dysfunction by inhibiting Nrf2/Keap1 signaling |
| title_full | Cadmium exposure promotes thyroid pyroptosis and endocrine dysfunction by inhibiting Nrf2/Keap1 signaling |
| title_fullStr | Cadmium exposure promotes thyroid pyroptosis and endocrine dysfunction by inhibiting Nrf2/Keap1 signaling |
| title_full_unstemmed | Cadmium exposure promotes thyroid pyroptosis and endocrine dysfunction by inhibiting Nrf2/Keap1 signaling |
| title_short | Cadmium exposure promotes thyroid pyroptosis and endocrine dysfunction by inhibiting Nrf2/Keap1 signaling |
| title_sort | cadmium exposure promotes thyroid pyroptosis and endocrine dysfunction by inhibiting nrf2 keap1 signaling |
| topic | Cadmium Thyroid Endocrine dysfunction Pyroptosis Nrf2/Keap1 signaling |
| url | http://www.sciencedirect.com/science/article/pii/S0147651322012167 |
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