Astaxanthin activates the Nrf2/Keap1/HO-1 pathway to inhibit oxidative stress and ferroptosis, reducing triphenyl phosphate (TPhP)-induced neurodevelopmental toxicity
Triphenyl phosphate (TPhP) serves as a major organophosphorus flame retardant, and its induced neurodevelopmental toxicity has attracted widespread attention, but the mechanism remains unclear. In this study, we involved zebrafish to explore the new mechanism of TPhP inducing oxidative stress and fe...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-02-01
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| Series: | Ecotoxicology and Environmental Safety |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651324000356 |
| _version_ | 1797328839826735104 |
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| author | Qiong Zhang Congying Luo Zhikang Li Wenlong Huang Shukai Zheng Caixia Liu Xiaoling Shi Yikai Ma Qingqing Ni Wei Tan Jiajun Peng Yuequn Chen Wenying Wu Jiejie Li Kusheng Wu |
| author_facet | Qiong Zhang Congying Luo Zhikang Li Wenlong Huang Shukai Zheng Caixia Liu Xiaoling Shi Yikai Ma Qingqing Ni Wei Tan Jiajun Peng Yuequn Chen Wenying Wu Jiejie Li Kusheng Wu |
| author_sort | Qiong Zhang |
| collection | DOAJ |
| description | Triphenyl phosphate (TPhP) serves as a major organophosphorus flame retardant, and its induced neurodevelopmental toxicity has attracted widespread attention, but the mechanism remains unclear. In this study, we involved zebrafish to explore the new mechanism of TPhP inducing oxidative stress and ferroptosis to promote neurodevelopmental toxicity. The results suggested that TPhP affected the embryonic development, reduced the number of new neurons, and led to abnormal neural behavior in zebrafish larvae. TPhP also induced ROS accumulation, activated the antioxidant defense signal Nrf2 and Keap1, and significantly changed the activities of Acetylcholinesterase (AChE), Adenosine triphosphatase (ATPase) and glutathione S-transferase (GST). In addition, TPhP induced ferroptosis in zebrafish, which was reflected in the increase of Fe2+ content, the abnormal expression of GPX4 protein and genes related to iron metabolism (gpx4a, slc7a11, acsl4b, tfa, slc40a1, fth1b, tfr2, tfr1a, tfr1b and ncoa4). Astaxanthin intervention specifically inhibited ROS levels, and reversed SLC7A11 and GPX4 expression levels and Fe2+ metabolism thus alleviating ferroptosis induced by TPhP. Astaxanthin also partially reversed the activity of AChE, GST and the expression of neurodevelopmental-related genes (gap43, gfap, neurog1 and syn2a), so as to partially rescue the embryonic developmental abnormalities and motor behavior disorders induced by TPhP. More interestingly, the expression of mitochondrial apoptosis-related protein BAX, anti-apoptotic protein BCL-2, Caspase3 and Caspase9 was significantly altered in the TPhP exposed group, which could be also reversed by Astaxanthin intervention. In summary, our results suggested that TPhP exposure can induce oxidative stress and ferroptosis, thereby causing neurodevelopment toxicity to zebrafish, while Astaxanthin can partially reverse oxidative stress and reduce the neurodevelopmental toxicity of zebrafish larvae by activating Nrf2/Keap1/HO-1 signaling pathway. |
| first_indexed | 2024-03-08T06:56:44Z |
| format | Article |
| id | doaj.art-3d6944af090748c1b2911bd0b87f90fa |
| institution | Directory Open Access Journal |
| issn | 0147-6513 |
| language | English |
| last_indexed | 2024-03-08T06:56:44Z |
| publishDate | 2024-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ecotoxicology and Environmental Safety |
| spelling | doaj.art-3d6944af090748c1b2911bd0b87f90fa2024-02-03T06:34:26ZengElsevierEcotoxicology and Environmental Safety0147-65132024-02-01271115960Astaxanthin activates the Nrf2/Keap1/HO-1 pathway to inhibit oxidative stress and ferroptosis, reducing triphenyl phosphate (TPhP)-induced neurodevelopmental toxicityQiong Zhang0Congying Luo1Zhikang Li2Wenlong Huang3Shukai Zheng4Caixia Liu5Xiaoling Shi6Yikai Ma7Qingqing Ni8Wei Tan9Jiajun Peng10Yuequn Chen11Wenying Wu12Jiejie Li13Kusheng Wu14Department of Preventive Medicine, Shantou University Medical College, Shantou 515041, Guangdong, ChinaDepartment of Preventive Medicine, Shantou University Medical College, Shantou 515041, Guangdong, ChinaDepartment of Preventive Medicine, Shantou University Medical College, Shantou 515041, Guangdong, ChinaDepartment of Forensic Medicine, Shantou University Medical College, Shantou 515041, Guangdong, ChinaDepartment of Burns and Plastic Surgery, The Second Affiliated Hospital of Shantou University Medical College, Shantou 515041, Guangdong, ChinaDepartment of Preventive Medicine, Shantou University Medical College, Shantou 515041, Guangdong, ChinaDepartment of Preventive Medicine, Shantou University Medical College, Shantou 515041, Guangdong, ChinaDepartment of Preventive Medicine, Shantou University Medical College, Shantou 515041, Guangdong, ChinaDepartment of Preventive Medicine, Shantou University Medical College, Shantou 515041, Guangdong, ChinaDepartment of Preventive Medicine, Shantou University Medical College, Shantou 515041, Guangdong, ChinaDepartment of Preventive Medicine, Shantou University Medical College, Shantou 515041, Guangdong, ChinaDepartment of Preventive Medicine, Shantou University Medical College, Shantou 515041, Guangdong, ChinaDepartment of Preventive Medicine, Shantou University Medical College, Shantou 515041, Guangdong, ChinaDepartment of Preventive Medicine, Shantou University Medical College, Shantou 515041, Guangdong, ChinaDepartment of Preventive Medicine, Shantou University Medical College, Shantou 515041, Guangdong, China; Correspondence to: Department of Preventive Medicine, Shantou University Medical College, No.22, Xinling Rd., Shantou 515041, Guangdong, China.Triphenyl phosphate (TPhP) serves as a major organophosphorus flame retardant, and its induced neurodevelopmental toxicity has attracted widespread attention, but the mechanism remains unclear. In this study, we involved zebrafish to explore the new mechanism of TPhP inducing oxidative stress and ferroptosis to promote neurodevelopmental toxicity. The results suggested that TPhP affected the embryonic development, reduced the number of new neurons, and led to abnormal neural behavior in zebrafish larvae. TPhP also induced ROS accumulation, activated the antioxidant defense signal Nrf2 and Keap1, and significantly changed the activities of Acetylcholinesterase (AChE), Adenosine triphosphatase (ATPase) and glutathione S-transferase (GST). In addition, TPhP induced ferroptosis in zebrafish, which was reflected in the increase of Fe2+ content, the abnormal expression of GPX4 protein and genes related to iron metabolism (gpx4a, slc7a11, acsl4b, tfa, slc40a1, fth1b, tfr2, tfr1a, tfr1b and ncoa4). Astaxanthin intervention specifically inhibited ROS levels, and reversed SLC7A11 and GPX4 expression levels and Fe2+ metabolism thus alleviating ferroptosis induced by TPhP. Astaxanthin also partially reversed the activity of AChE, GST and the expression of neurodevelopmental-related genes (gap43, gfap, neurog1 and syn2a), so as to partially rescue the embryonic developmental abnormalities and motor behavior disorders induced by TPhP. More interestingly, the expression of mitochondrial apoptosis-related protein BAX, anti-apoptotic protein BCL-2, Caspase3 and Caspase9 was significantly altered in the TPhP exposed group, which could be also reversed by Astaxanthin intervention. In summary, our results suggested that TPhP exposure can induce oxidative stress and ferroptosis, thereby causing neurodevelopment toxicity to zebrafish, while Astaxanthin can partially reverse oxidative stress and reduce the neurodevelopmental toxicity of zebrafish larvae by activating Nrf2/Keap1/HO-1 signaling pathway.http://www.sciencedirect.com/science/article/pii/S0147651324000356Triphenyl phosphate (TPhP)NeurotoxicityNrf2/Keap1/HO-1 signaling pathwayAstaxanthinZebrafish |
| spellingShingle | Qiong Zhang Congying Luo Zhikang Li Wenlong Huang Shukai Zheng Caixia Liu Xiaoling Shi Yikai Ma Qingqing Ni Wei Tan Jiajun Peng Yuequn Chen Wenying Wu Jiejie Li Kusheng Wu Astaxanthin activates the Nrf2/Keap1/HO-1 pathway to inhibit oxidative stress and ferroptosis, reducing triphenyl phosphate (TPhP)-induced neurodevelopmental toxicity Ecotoxicology and Environmental Safety Triphenyl phosphate (TPhP) Neurotoxicity Nrf2/Keap1/HO-1 signaling pathway Astaxanthin Zebrafish |
| title | Astaxanthin activates the Nrf2/Keap1/HO-1 pathway to inhibit oxidative stress and ferroptosis, reducing triphenyl phosphate (TPhP)-induced neurodevelopmental toxicity |
| title_full | Astaxanthin activates the Nrf2/Keap1/HO-1 pathway to inhibit oxidative stress and ferroptosis, reducing triphenyl phosphate (TPhP)-induced neurodevelopmental toxicity |
| title_fullStr | Astaxanthin activates the Nrf2/Keap1/HO-1 pathway to inhibit oxidative stress and ferroptosis, reducing triphenyl phosphate (TPhP)-induced neurodevelopmental toxicity |
| title_full_unstemmed | Astaxanthin activates the Nrf2/Keap1/HO-1 pathway to inhibit oxidative stress and ferroptosis, reducing triphenyl phosphate (TPhP)-induced neurodevelopmental toxicity |
| title_short | Astaxanthin activates the Nrf2/Keap1/HO-1 pathway to inhibit oxidative stress and ferroptosis, reducing triphenyl phosphate (TPhP)-induced neurodevelopmental toxicity |
| title_sort | astaxanthin activates the nrf2 keap1 ho 1 pathway to inhibit oxidative stress and ferroptosis reducing triphenyl phosphate tphp induced neurodevelopmental toxicity |
| topic | Triphenyl phosphate (TPhP) Neurotoxicity Nrf2/Keap1/HO-1 signaling pathway Astaxanthin Zebrafish |
| url | http://www.sciencedirect.com/science/article/pii/S0147651324000356 |
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