Fipronil Triggers Immunotoxicity Through Reactive Oxygen Species-Driven Mitochondrial Apoptosis in Thymocytes
Fipronil (FPN), a widely used pesticide, is associated with significant immunotoxic effects, particularly impacting thymocyte survival and immune homeostasis. This study explores the mechanistic pathways underlying FPN-induced apoptosis and oxidative stress. Short-term FPN exposure (1–10 mg/kg) nota...
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MDPI AG
2025-03-01
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| author | Jui-Fang Kuo Yai-Ping Hsiao Yao-De Wang Hsin-Pei Weng Chia-Chi Wang |
| author_facet | Jui-Fang Kuo Yai-Ping Hsiao Yao-De Wang Hsin-Pei Weng Chia-Chi Wang |
| author_sort | Jui-Fang Kuo |
| collection | DOAJ |
| description | Fipronil (FPN), a widely used pesticide, is associated with significant immunotoxic effects, particularly impacting thymocyte survival and immune homeostasis. This study explores the mechanistic pathways underlying FPN-induced apoptosis and oxidative stress. Short-term FPN exposure (1–10 mg/kg) notably suppressed the expression of both anti-apoptotic (<i>Bcl-2</i>, <i>Bcl-6</i>, <i>Mcl-1</i>) and pro-apoptotic (<i>Bnip3</i>, <i>Bim</i>) genes in thymic tissues in vivo. Additionally, in isolated primary thymocytes, FPN directly decreased the expression of <i>Bcl-2</i>, <i>Bcl-6</i>, <i>Mcl-1</i>, and <i>Bnip3</i> expression, coupled with a significant increase in pro-apoptotic <i>Bim</i> expression in a dose-dependent manner. FPN treatment directly led to elevated reactive oxygen species (ROS), lipid peroxidation, mitochondrial membrane depolarization, reduced cellular metabolic activity, and depleted intracellular calcium and glutathione (GSH) levels, indicating mitochondrial dysfunction and oxidative stress. Annexin V/PI staining confirmed that FPN induced late-stage apoptosis and necrosis in primary thymocytes. These findings elucidate the immunotoxic effects of FPN on thymocytes, highlighting its detrimental impact on immune system integrity, thymic development, and T cell maturation through oxidative damage and mitochondrial-mediated apoptosis. |
| format | Article |
| id | doaj-art-8d4dc48f293d415595fa26196ffdd1d9 |
| institution | OA Journals |
| issn | 2305-6304 |
| language | English |
| publishDate | 2025-03-01 |
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| spelling | doaj-art-8d4dc48f293d415595fa26196ffdd1d92025-08-20T01:49:00ZengMDPI AGToxics2305-63042025-03-0113320410.3390/toxics13030204Fipronil Triggers Immunotoxicity Through Reactive Oxygen Species-Driven Mitochondrial Apoptosis in ThymocytesJui-Fang Kuo0Yai-Ping Hsiao1Yao-De Wang2Hsin-Pei Weng3Chia-Chi Wang4School of Veterinary Medicine, National Taiwan University, Taipei 106, TaiwanDepartment of Biochemistry and Molecular Medicine, UC Davis Comprehensive Cancer Center, University of California Davis, Sacramento, CA 95817, USASchool of Veterinary Medicine, National Taiwan University, Taipei 106, TaiwanSchool of Veterinary Medicine, National Taiwan University, Taipei 106, TaiwanSchool of Veterinary Medicine, National Taiwan University, Taipei 106, TaiwanFipronil (FPN), a widely used pesticide, is associated with significant immunotoxic effects, particularly impacting thymocyte survival and immune homeostasis. This study explores the mechanistic pathways underlying FPN-induced apoptosis and oxidative stress. Short-term FPN exposure (1–10 mg/kg) notably suppressed the expression of both anti-apoptotic (<i>Bcl-2</i>, <i>Bcl-6</i>, <i>Mcl-1</i>) and pro-apoptotic (<i>Bnip3</i>, <i>Bim</i>) genes in thymic tissues in vivo. Additionally, in isolated primary thymocytes, FPN directly decreased the expression of <i>Bcl-2</i>, <i>Bcl-6</i>, <i>Mcl-1</i>, and <i>Bnip3</i> expression, coupled with a significant increase in pro-apoptotic <i>Bim</i> expression in a dose-dependent manner. FPN treatment directly led to elevated reactive oxygen species (ROS), lipid peroxidation, mitochondrial membrane depolarization, reduced cellular metabolic activity, and depleted intracellular calcium and glutathione (GSH) levels, indicating mitochondrial dysfunction and oxidative stress. Annexin V/PI staining confirmed that FPN induced late-stage apoptosis and necrosis in primary thymocytes. These findings elucidate the immunotoxic effects of FPN on thymocytes, highlighting its detrimental impact on immune system integrity, thymic development, and T cell maturation through oxidative damage and mitochondrial-mediated apoptosis.https://www.mdpi.com/2305-6304/13/3/204fipronilimmunotoxicityapoptosisBCL-2 familyreactive oxygen speciesmitochondrial membrane potential |
| spellingShingle | Jui-Fang Kuo Yai-Ping Hsiao Yao-De Wang Hsin-Pei Weng Chia-Chi Wang Fipronil Triggers Immunotoxicity Through Reactive Oxygen Species-Driven Mitochondrial Apoptosis in Thymocytes Toxics fipronil immunotoxicity apoptosis BCL-2 family reactive oxygen species mitochondrial membrane potential |
| title | Fipronil Triggers Immunotoxicity Through Reactive Oxygen Species-Driven Mitochondrial Apoptosis in Thymocytes |
| title_full | Fipronil Triggers Immunotoxicity Through Reactive Oxygen Species-Driven Mitochondrial Apoptosis in Thymocytes |
| title_fullStr | Fipronil Triggers Immunotoxicity Through Reactive Oxygen Species-Driven Mitochondrial Apoptosis in Thymocytes |
| title_full_unstemmed | Fipronil Triggers Immunotoxicity Through Reactive Oxygen Species-Driven Mitochondrial Apoptosis in Thymocytes |
| title_short | Fipronil Triggers Immunotoxicity Through Reactive Oxygen Species-Driven Mitochondrial Apoptosis in Thymocytes |
| title_sort | fipronil triggers immunotoxicity through reactive oxygen species driven mitochondrial apoptosis in thymocytes |
| topic | fipronil immunotoxicity apoptosis BCL-2 family reactive oxygen species mitochondrial membrane potential |
| url | https://www.mdpi.com/2305-6304/13/3/204 |
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