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...

Full description

Saved in:
Bibliographic Details
Main Authors: Leisheng Wang, Yifei Fu, Shiwei Xu, Enhong Chen, Shuo Zhang, Dongjie Yang, Youzhao He, Yuanlong Gu, Yong Mao, Fenglai Yuan, Hao Hu
Format: Article
Language:English
Published: Elsevier 2025-09-01
Series:Ecotoxicology and Environmental Safety
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S0147651325010565
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0147-6513