Complex immunotoxic effects of T-2 Toxin on the murine spleen and thymus: Oxidative damage, inflammasomes, apoptosis, and immunosuppression
T-2 toxin (T-2), a highly stable and toxic mycotoxin, poses a significant public health risk as an inevitable environmental pollutant. However, the mechanisms behind its immunotoxic and immunosuppressive effects are not fully understood. For this study, sixty healthy 4-week-old male C57BL/6 N mice w...
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Elsevier
2025-01-01
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| Series: | Ecotoxicology and Environmental Safety |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651324015525 |
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| author | Mingyan Chen Yanfang Zhang Yangbo Zhao Kewei Cao Ruiyan Niu Dongguang Guo Zilong Sun |
| author_facet | Mingyan Chen Yanfang Zhang Yangbo Zhao Kewei Cao Ruiyan Niu Dongguang Guo Zilong Sun |
| author_sort | Mingyan Chen |
| collection | DOAJ |
| description | T-2 toxin (T-2), a highly stable and toxic mycotoxin, poses a significant public health risk as an inevitable environmental pollutant. However, the mechanisms behind its immunotoxic and immunosuppressive effects are not fully understood. For this study, sixty healthy 4-week-old male C57BL/6 N mice were divided randomly into four groups and treated for 28 days with T-2 concentrations of 0, 0.5, 1.0, and 2.0 mg/kg. Our findings revealed significant damage to the thymus and spleen that was proportional to the dose administered, as evidenced by changes in organ indices and histopathological abnormalities. We observed mitochondrial swelling, chromatin condensation, and nuclear structure disruptions in these organs. Even at low doses (0.5 mg/kg), T-2 administration resulted in significant immunosuppression, as evidenced by disturbed blood parameters and altered CD4 + /CD8 + ratios. Elevated ROS and MDA levels indicate oxidative damage, whereas SOD, T-AOC, CAT, and GSH levels are reduced in both the thymus and spleen. Furthermore, the levels of NLRP3, ASC, caspase-1, and IL-1β proteins were significantly elevated, indicating the activation of the NLRP3 inflammasome pathway. Additionally, activation of the apoptosis pathway was demonstrated by an increased Bax/Bcl-2 ratio and heightened activation of caspase-3 and −9. Transcriptomic analysis elucidated the pivotal role of mitochondrial pathways in T-2-induced immunotoxicity. This study elucidates the significant immunotoxic effects of T-2 on the murine spleen and thymus, detailing the underlying mechanisms of T-2-induced immunosuppression. The key mechanisms identified include oxidative stress, activation of the NLRP3 inflammasome, apoptosis, and mitochondrial dysfunction. These findings reveal critical pathways through which T-2 impairs immune system functionality and provide a basis for developing targeted therapeutic strategies to mitigate its immunotoxic effects. |
| format | Article |
| id | doaj-art-ac8f897ae0664514b6f3796874ca2b1a |
| institution | Kabale University |
| issn | 0147-6513 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ecotoxicology and Environmental Safety |
| spelling | doaj-art-ac8f897ae0664514b6f3796874ca2b1a2025-01-23T05:25:42ZengElsevierEcotoxicology and Environmental Safety0147-65132025-01-01289117476Complex immunotoxic effects of T-2 Toxin on the murine spleen and thymus: Oxidative damage, inflammasomes, apoptosis, and immunosuppressionMingyan Chen0Yanfang Zhang1Yangbo Zhao2Kewei Cao3Ruiyan Niu4Dongguang Guo5Zilong Sun6College of Veterinary Medicine, Shanxi Agricultural University, Jinzhong, Shanxi 030801, ChinaSchool of Biological Engineering, Xinxiang University, Xinxiang, Henan 453000, ChinaCollege of Veterinary Medicine, Shanxi Agricultural University, Jinzhong, Shanxi 030801, ChinaCollege of Veterinary Medicine, Shanxi Agricultural University, Jinzhong, Shanxi 030801, ChinaCollege of Veterinary Medicine, Shanxi Agricultural University, Jinzhong, Shanxi 030801, ChinaSchool of Biological Engineering, Xinxiang University, Xinxiang, Henan 453000, China; Corresponding authors.College of Veterinary Medicine, Shanxi Agricultural University, Jinzhong, Shanxi 030801, China; Corresponding authors.T-2 toxin (T-2), a highly stable and toxic mycotoxin, poses a significant public health risk as an inevitable environmental pollutant. However, the mechanisms behind its immunotoxic and immunosuppressive effects are not fully understood. For this study, sixty healthy 4-week-old male C57BL/6 N mice were divided randomly into four groups and treated for 28 days with T-2 concentrations of 0, 0.5, 1.0, and 2.0 mg/kg. Our findings revealed significant damage to the thymus and spleen that was proportional to the dose administered, as evidenced by changes in organ indices and histopathological abnormalities. We observed mitochondrial swelling, chromatin condensation, and nuclear structure disruptions in these organs. Even at low doses (0.5 mg/kg), T-2 administration resulted in significant immunosuppression, as evidenced by disturbed blood parameters and altered CD4 + /CD8 + ratios. Elevated ROS and MDA levels indicate oxidative damage, whereas SOD, T-AOC, CAT, and GSH levels are reduced in both the thymus and spleen. Furthermore, the levels of NLRP3, ASC, caspase-1, and IL-1β proteins were significantly elevated, indicating the activation of the NLRP3 inflammasome pathway. Additionally, activation of the apoptosis pathway was demonstrated by an increased Bax/Bcl-2 ratio and heightened activation of caspase-3 and −9. Transcriptomic analysis elucidated the pivotal role of mitochondrial pathways in T-2-induced immunotoxicity. This study elucidates the significant immunotoxic effects of T-2 on the murine spleen and thymus, detailing the underlying mechanisms of T-2-induced immunosuppression. The key mechanisms identified include oxidative stress, activation of the NLRP3 inflammasome, apoptosis, and mitochondrial dysfunction. These findings reveal critical pathways through which T-2 impairs immune system functionality and provide a basis for developing targeted therapeutic strategies to mitigate its immunotoxic effects.http://www.sciencedirect.com/science/article/pii/S0147651324015525T-2 toxinImmunotoxicityOxidative damageNLRP3 inflammasomeMitochondrial pathway |
| spellingShingle | Mingyan Chen Yanfang Zhang Yangbo Zhao Kewei Cao Ruiyan Niu Dongguang Guo Zilong Sun Complex immunotoxic effects of T-2 Toxin on the murine spleen and thymus: Oxidative damage, inflammasomes, apoptosis, and immunosuppression Ecotoxicology and Environmental Safety T-2 toxin Immunotoxicity Oxidative damage NLRP3 inflammasome Mitochondrial pathway |
| title | Complex immunotoxic effects of T-2 Toxin on the murine spleen and thymus: Oxidative damage, inflammasomes, apoptosis, and immunosuppression |
| title_full | Complex immunotoxic effects of T-2 Toxin on the murine spleen and thymus: Oxidative damage, inflammasomes, apoptosis, and immunosuppression |
| title_fullStr | Complex immunotoxic effects of T-2 Toxin on the murine spleen and thymus: Oxidative damage, inflammasomes, apoptosis, and immunosuppression |
| title_full_unstemmed | Complex immunotoxic effects of T-2 Toxin on the murine spleen and thymus: Oxidative damage, inflammasomes, apoptosis, and immunosuppression |
| title_short | Complex immunotoxic effects of T-2 Toxin on the murine spleen and thymus: Oxidative damage, inflammasomes, apoptosis, and immunosuppression |
| title_sort | complex immunotoxic effects of t 2 toxin on the murine spleen and thymus oxidative damage inflammasomes apoptosis and immunosuppression |
| topic | T-2 toxin Immunotoxicity Oxidative damage NLRP3 inflammasome Mitochondrial pathway |
| url | http://www.sciencedirect.com/science/article/pii/S0147651324015525 |
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