Exposure to dimethyl phthalate induces oxidative stress and autophagy in gill of Zebrafish via the PI3K/AKT/mTOR pathway: Protective role of 1,8-cineole

Dimethyl phthalate (DMP), a widespread environmental pollutant, poses serious risks to aquatic organisms. This study investigated the mechanisms of DMP-induced oxidative stress and autophagy in zebrafish gill tissues, and evaluated the protective effect of 1,8-cineole. Zebrafish models were established for DMP exposure alone, 1,8-cineole treatment alone, and combined exposure. Using histopathology, transmission electron microscopy, fluorescence staining, antioxidant enzyme activity assays, real-time quantitative PCR, and Western blot, we systematically analyzed the impacts of DMP on gill morphology, oxidative stress levels, autophagy-related gene and protein expression, and the PI3K/AKT/mTOR signaling pathway. Results revealed that DMP exposure significantly induced oxidative stress and autophagy in gill tissues and suppressed PI3K/AKT/mTOR pathway activity. In contrast, 1,8-cineole treatment effectively alleviated DMP-induced oxidative damage and autophagy activation, while partially restoring PI3K/AKT/mTOR signaling. This study is the first to demonstrate that 1,8-cineole mitigates DMP-induced autophagy injury in gills by modulating the PI3K/AKT/mTOR pathway, offering a theoretical foundation and a potential green strategy for protecting aquatic organisms from phthalate toxicity.