An integrated approach for evaluating the interactive effects between azoxystrobin and ochratoxin A: Pathway-based in vivo analyses

Azoxystrobin (AZO) is a broad-spectrum strobilurin fungicide widely used in agriculture. However, its use increases the possibility of co-occurrence with mycotoxins such as ochratoxin A (OTA), which poses a significant risk to human health. Therefore, it is imperative to prioritize the evaluation of the combined toxicity of these two compounds. To assess the combined effects of AZO and OTA, the response genes and phenotypes for AZO or OTA exposure were obtained by utilizing Comparative Toxicogenomics Database, and Database for Annotation, Visualization and Integrated Discovery was used for GO and KEGG pathway enrichment analysis. In addition, we provided in-vivo evidence that AZO and OTA, in isolation and combination, could disrupt a variety of biological processes, such as oxidative stress, inflammatory response, apoptosis and thyroid hormone regulation under environmentally relevant concentrations. Notably, our findings suggest that the combined exposure group exhibited greater toxicity, as evidenced by the expression of various markers associated with the aforementioned biological processes, compared to the individual exposure group, which presents potential targets for the underlying mechanisms of induced toxicity. This study provides a novel methodological approach for exploring the mechanism of combined toxicity of a fungicide and a mycotoxin, which can shed light for conducting risk assessment of foodborne toxins.