Targeting the PI3K-AKT pathway to alleviate 6PPDQ-induced cognitive impairment associated with metabolic syndrome
6PPD-quinone (6PPDQ), a derivative of the antioxidant 6PPD used in the rubber industry, has been implicated in environmental and public health risks. To explore its impact on metabolic and cognitive functions, we orally administered 6PPDQ to mice and assessed its effects. Our results show that 6PPDQ...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-09-01
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| Series: | Ecotoxicology and Environmental Safety |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651325010565 |
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| author | Leisheng Wang Yifei Fu Shiwei Xu Enhong Chen Shuo Zhang Dongjie Yang Youzhao He Yuanlong Gu Yong Mao Fenglai Yuan Hao Hu |
| author_facet | Leisheng Wang Yifei Fu Shiwei Xu Enhong Chen Shuo Zhang Dongjie Yang Youzhao He Yuanlong Gu Yong Mao Fenglai Yuan Hao Hu |
| author_sort | Leisheng Wang |
| collection | DOAJ |
| description | 6PPD-quinone (6PPDQ), a derivative of the antioxidant 6PPD used in the rubber industry, has been implicated in environmental and public health risks. To explore its impact on metabolic and cognitive functions, we orally administered 6PPDQ to mice and assessed its effects. Our results show that 6PPDQ induces a dose-dependent increase in body weight, elevated fasting blood glucose, insulin resistance, and other hallmarks of metabolic syndrome. Furthermore, cognitive tests revealed significant impairments in learning and memory in 6PPDQ-treated mice. Transcriptomic and Western blot analyses suggest that 6PPDQ disrupts insulin signaling through inhibition of the PI3K-AKT pathway, leading to metabolic and cognitive dysfunction. Notably, treatment with the PI3K-AKT agonist SC79 partially alleviated these effects. These findings highlight the health risks of 6PPDQ exposure and suggest potential avenues for preventive and therapeutic strategies. |
| format | Article |
| id | doaj-art-05906009065a4e53bb8b4c9d82e96867 |
| institution | Kabale University |
| issn | 0147-6513 |
| language | English |
| publishDate | 2025-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ecotoxicology and Environmental Safety |
| spelling | doaj-art-05906009065a4e53bb8b4c9d82e968672025-08-20T03:41:53ZengElsevierEcotoxicology and Environmental Safety0147-65132025-09-0130211871110.1016/j.ecoenv.2025.118711Targeting the PI3K-AKT pathway to alleviate 6PPDQ-induced cognitive impairment associated with metabolic syndromeLeisheng Wang0Yifei Fu1Shiwei Xu2Enhong Chen3Shuo Zhang4Dongjie Yang5Youzhao He6Yuanlong Gu7Yong Mao8Fenglai Yuan9Hao Hu10Affiliated Hospital of Jiangnan University, Wuxi 214122, China; Wuxi Medical College, Jiangnan University, Wuxi 214122, China; Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200336, ChinaAffiliated Hospital of Jiangnan University, Wuxi 214122, China; Wuxi Medical College, Jiangnan University, Wuxi 214122, ChinaAffiliated Hospital of Jiangnan University, Wuxi 214122, China; Wuxi Medical College, Jiangnan University, Wuxi 214122, ChinaAffiliated Hospital of Jiangnan University, Wuxi 214122, ChinaAffiliated Hospital of Jiangnan University, Wuxi 214122, ChinaAffiliated Hospital of Jiangnan University, Wuxi 214122, ChinaAffiliated Hospital of Jiangnan University, Wuxi 214122, ChinaAffiliated Hospital of Jiangnan University, Wuxi 214122, ChinaAffiliated Hospital of Jiangnan University, Wuxi 214122, China; Wuxi Medical College, Jiangnan University, Wuxi 214122, China; Corresponding authors at: Affiliated Hospital of Jiangnan University, Wuxi 214122, China.Affiliated Hospital of Jiangnan University, Wuxi 214122, China; Wuxi Medical College, Jiangnan University, Wuxi 214122, China; Corresponding authors at: Affiliated Hospital of Jiangnan University, Wuxi 214122, China.Affiliated Hospital of Jiangnan University, Wuxi 214122, China; Wuxi Medical College, Jiangnan University, Wuxi 214122, China; Corresponding authors at: Affiliated Hospital of Jiangnan University, Wuxi 214122, China.6PPD-quinone (6PPDQ), a derivative of the antioxidant 6PPD used in the rubber industry, has been implicated in environmental and public health risks. To explore its impact on metabolic and cognitive functions, we orally administered 6PPDQ to mice and assessed its effects. Our results show that 6PPDQ induces a dose-dependent increase in body weight, elevated fasting blood glucose, insulin resistance, and other hallmarks of metabolic syndrome. Furthermore, cognitive tests revealed significant impairments in learning and memory in 6PPDQ-treated mice. Transcriptomic and Western blot analyses suggest that 6PPDQ disrupts insulin signaling through inhibition of the PI3K-AKT pathway, leading to metabolic and cognitive dysfunction. Notably, treatment with the PI3K-AKT agonist SC79 partially alleviated these effects. These findings highlight the health risks of 6PPDQ exposure and suggest potential avenues for preventive and therapeutic strategies.http://www.sciencedirect.com/science/article/pii/S01476513250105656PPD-quinoneMetabolic syndromeCognitive impairment |
| spellingShingle | Leisheng Wang Yifei Fu Shiwei Xu Enhong Chen Shuo Zhang Dongjie Yang Youzhao He Yuanlong Gu Yong Mao Fenglai Yuan Hao Hu Targeting the PI3K-AKT pathway to alleviate 6PPDQ-induced cognitive impairment associated with metabolic syndrome Ecotoxicology and Environmental Safety 6PPD-quinone Metabolic syndrome Cognitive impairment |
| title | Targeting the PI3K-AKT pathway to alleviate 6PPDQ-induced cognitive impairment associated with metabolic syndrome |
| title_full | Targeting the PI3K-AKT pathway to alleviate 6PPDQ-induced cognitive impairment associated with metabolic syndrome |
| title_fullStr | Targeting the PI3K-AKT pathway to alleviate 6PPDQ-induced cognitive impairment associated with metabolic syndrome |
| title_full_unstemmed | Targeting the PI3K-AKT pathway to alleviate 6PPDQ-induced cognitive impairment associated with metabolic syndrome |
| title_short | Targeting the PI3K-AKT pathway to alleviate 6PPDQ-induced cognitive impairment associated with metabolic syndrome |
| title_sort | targeting the pi3k akt pathway to alleviate 6ppdq induced cognitive impairment associated with metabolic syndrome |
| topic | 6PPD-quinone Metabolic syndrome Cognitive impairment |
| url | http://www.sciencedirect.com/science/article/pii/S0147651325010565 |
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