Alternariol, a Mycotoxin, Induces Oxidative Stress, Inflammation, and Apoptosis in Human Astrocytes: Protective Effects of Eicosapentaenoic Acid

Alternariol (AOH), a mycotoxin produced by Alternaria species, has been associated with oxidative and inflammatory toxicity, although its effects on astrocytes remain poorly understood. This study investigated AOH-induced cellular responses and the protective effects of eicosapentaenoic acid (EPA) in human astrocytes. Exposure to AOH (25-125 μM) reduced cell viability, increased intracellular reactive oxygen species (ROS) production, depleted glutathione (GSH), and elevated the expression of pro-inflammatory cytokines, including TNF-α, IL-1β, and IL-6. AOH also induced apoptosis-related molecular alterations, characterized by increased Bax, cleaved caspase-9, and cleaved caspase-3 expression together with reduced Bcl-2 levels. In addition, AOH modulated the expression of Nrf2 and its downstream antioxidant targets, heme oxygenase-1 (HO-1) and NAD(P)H oxidoreductase 1 (NQO1), suggesting involvement of antioxidant defense-related signaling. Pretreatment with EPA (5 μM) significantly attenuated AOH-induced oxidative stress, inflammatory responses, and apoptosis-related molecular changes. These findings further identify astrocytes as a sensitive cellular target of Alternaria mycotoxins. Collectively, the findings indicate that AOH disrupts redox homeostasis and promotes cellular stress responses in human astrocytes, whereas EPA mitigates these effects and helps maintain cellular homeostasis.