Exploration of beauvericin's toxic effects and mechanisms in human astrocytes and N-acetylcysteine's protective role

• Published in: Toxicon (Oxford) 2024-05, Vol.243, p.107734-107734, Article 107734
• Main Authors: Liang, Wei-Zhe, Chia, Yuan-Yi, Sun, Huai-Jhih, Sun, Gwo‐Ching
• Format: Article
• Language: English
• Subjects: Apoptosis; Astrocytes; Beauvericin; Mycotoxin; N-acetylcysteine; Oxidative stress
• ISSN: 0041-0101; 1879-3150
• DOI: 10.1016/j.toxicon.2024.107734

Beauvericin (BEA) is a newly identified mycotoxin produced by various Fusarium species, and its contamination in food and animal feed is widespread globally. This mycotoxin demonstrates cytotoxic effects by inducing oxidative stress in multiple models. Furthermore, evidence indicates that BEA possesses diverse toxic activities, making it a promising candidate for toxicological research. Recent studies have highlighted the ability of BEA to traverse the blood-brain barrier, suggesting its potential neurotoxicity. However, limited information is available regarding the neurotoxic effects of BEA on human astrocytes. Therefore, this study aimed to assess the neurotoxic effects of BEA on the Gibco® Human Astrocyte (GHA) cell line and elucidate the underlying mechanisms. Additionally, the study aimed to investigate the protective effects of the antioxidant N-acetylcysteine (NAC) against BEA-induced toxicity. The data show that exposure to BEA within the 2.5–15 μM concentration range resulted in concentration-dependent cytotoxicity. BEA-treated cells exhibited significantly increased levels of reactive oxygen species (ROS), while intracellular glutathione (GSH) content was significantly reduced. Western blot analysis of cells treated with BEA revealed altered protein levels of Bax, cleaved caspase-9, and caspase-3, along with an increased Bax/Bcl-2 ratio, indicating the induction of apoptosis. Additionally, BEA exposure triggered antioxidant responses, as evidenced by increased protein expression of Nrf2, HO-1, and NQO1. Significantly, pretreatment with NAC partially attenuated the significant toxic effects of BEA. In conclusion, our findings suggest that BEA-induced cytotoxicity in GHA cells involves oxidative stress-associated apoptosis. Furthermore, NAC demonstrates potential as a protective agent against BEA-induced oxidative damage. [Display omitted] •Protective effects of N-acetylcysteine on neurotoxicity were explored in beauvericin-treated astrocytes.•In astrocytes, beauvericin induced apoptosis via oxidative stress.•In astrocytes, N-acetylcysteine inhibited beauvericin-induced apoptosis by regulating antioxidant signaling.