Acute and Subacute Oral Toxicity of Deoxynivalenol Exposure in a Dermatophagoides farinae-Induced Murine Asthma Model. (10th November 2020)

• Record Type: Journal Article
• Authors: Ookawara, Toa; Aihara, Ryota; Morimoto, Ai; Iwashita, Naoki; Kurata, Keigo; Takagi, Yoshiichi; Miyasaka, Atsushi; Kushiro, Masayo; Miyake, Shiro; Fukuyama, Tomoki
• Is Part Of: Toxicological sciences. Volume 179:Number 2(2021)
• Page Start: 229
• Page End: 240
• Publication Date: 2020-11-10
• Subjects: mycotoxin -- deoxynivalenol -- inflammation -- asthma -- Dermatophagoides farina -- IL-33 -- TSLP -- BALB/c mouse -- eoshinophil -- bronchial epithelial cell; Toxicology -- Periodicals; Toxicology -- Periodicals; Toxicology; Periodicals; 615.9
• DOI: 10.1093/toxsci/kfaa168
• Languages: English
• ISSNs: 1096-6080

Abstract

Abstract: Previously, researchers have demonstrated that mycotoxin deoxynivalenol (DON) significantly enhances immunocyte activation. However, the interaction between DON exposure and immune disorders remains unclear. In this study, we aimed to investigate whether acute and subacute oral exposure to DON exacerbates the development of respiratory allergy using a mite allergen ( Dermatophagoides farina, Derf)-induced mouse model of asthma. The direct relationship between DON exposure and asthma development was examined following acute oral DON administration (0, 0.1, or 0.3 mg/kg body weight), immediately before the final mite allergen challenge. Simultaneously, the influence of subacute oral exposure via low dose DON contaminated wheat (0.33 ppm) was evaluated using the same settings. To detect the proinflammatory effects of DON exposure, we examined the total and Derf-specific serum IgE levels, histology, number of immunocytes, and cytokine and chemokine secretion. Acute oral DON significantly enhanced the inflammatory responses, including cellular infiltration into bronchoalveolar lavage fluid, infiltration of immunocytes and cytokine production in local lymph nodes, and cytokine levels in lung tissues. Corresponding proinflammatory responses were observed in a mouse group exposed to subacute oral DON. In vivo results were validated by in vitro experiments using the human bronchial epithelial (BEAS-2B) and human eosinophilic leukemia (EOL-1) cell lines. Following exposure to DON, the secretion of interleukin (IL)-1β, IL-6, IL-8, and/or tumor necrosis factor-α in BEAS-2B cells, as well as EoL-1 cells, increased significantly. Our findings indicate that DON exposure is significantly involved in the proinflammatory response observed in respiratory allergy.