Evaluation of the mycotoxin patulin on cytotoxicity and oxidative stress in human glioblastoma cells and investigation of protective effect of the antioxidant N-acetylcysteine (NAC)

• Published in: Toxicon (Oxford) 2023-01, Vol.221, p.106957, Article 106957
• Main Authors: Hsu, Shu-Shong, Lin, Yung-Shang, Chio, Li-Min, Liang, Wei-Zhe
• Format: Article
• Language: English
• Subjects: Acetylcysteine - pharmacology; Antioxidant; Antioxidants - metabolism; Antioxidants - pharmacology; Apoptosis; Glioblastoma - drug therapy; Glioblastoma - metabolism; Human glioblastoma cells; Humans; Oxidative Stress; Patulin; Patulin - toxicity; Reactive Oxygen Species - metabolism; ROS
• ISSN: 0041-0101; 1879-3150
• DOI: 10.1016/j.toxicon.2022.106957

Mycotoxins are secondary metabolites produced by various kinds of fungi that can induce disease in humans. The fungal species Penicillium expansum produces patulin (C7H6O4), a polyketide lactone mycotoxin found in fruits. Patulin is classified as noncarcinogen; however, recently, it has been associated with harmful effects on the central nervous system. Patulin's toxic action has been established in various brain models; however, its effect on human glioblastoma remains elusive. This study explores whether patulin induces cytotoxicity through oxidative stress in DBTRG-05MG human glioblastoma cells. This study also evaluates whether the antioxidant N-acetylcysteine (NAC) protects against patulin-induced cytotoxicity. In DBTRG-05MG cells, patulin concentration (10–60 μM) dependently induced cytotoxicity. Concerning oxidative stress, patulin (10 and 20 μM) increased the production of intracellular reactive oxygen species (ROS) but depleted reduced glutathione (GSH) contents and regulated the expressions of antioxidant-related proteins (Nrf2 and HO-1). Furthermore, patulin induced cytotoxicity via modulation of apoptosis-related protein expressions (Bax, cleaved caspase-9, and cleaved caspase-3). These cytotoxic responses were partially reversed via pretreatment with NAC (10 μM). In summary, these data help us understand the toxicology of patulin in human glioblastoma and evaluate whether NAC could clinically reduce patulin-affected brain damage. [Display omitted] •Mechanism underlying the effect of patulin on cytotoxicity was explored in human glioblastoma cells.•Patulin induced cytotoxicity through oxidative stress-related apoptosis.•The antioxidant N-acetylcysteine significantly alleviated the patulin-induced oxidative stress and apoptosis.