Integrating in silico with in vivo approach to investigate phthalate and bisphenol A mixture-linked asthma development: Positive probiotic intervention

• Published in: Food and chemical toxicology 2021-12, Vol.158, p.112671-112671, Article 112671
• Main Authors: Baralić, Katarina, Bozic, Dragica, Živančević, Katarina, Milenković, Milan, Javorac, Dragana, Marić, Đurđica, Antonijević Miljaković, Evica, Buha Djordjevic, Aleksandra, Vukomanović, Predrag, Ćurčić, Marijana, Bulat, Zorica, Antonijević, Biljana, Đukić-Ćosić, Danijela
• Format: Article
• Language: English
• Subjects: Animals; Asthma; Asthma - chemically induced; Benzhydryl Compounds - toxicity; Computer Simulation; Endocrine disruptors; Endocrine Disruptors - toxicity; Humans; Kidney - drug effects; Lung - drug effects; Male; Mechanisms; Oxidative Stress - drug effects; Phenols - toxicity; Phthalic Acids - toxicity; Probiotic; Probiotics - pharmacology; Rats; Thymus Gland - drug effects; Toxicogenetics; Toxicogenomic data mining
• ISSN: 0278-6915; 1873-6351
• DOI: 10.1016/j.fct.2021.112671

The aim of this study was to explore the mechanisms of bis(2- ethylhexyl) phthalate (DEHP), dibutyl phthalate (DBP) and bisphenol A (BPA) mixture-induced asthma development and test probiotic as a potential positive intervention. Comparative Toxicogenomics Database (CTD) and ToppGene Suite were used as the main tools for in silico analysis. In vivo 28-day experiment was conducted on rats - seven groups (n = 6): (1) Control: corn oil, (2) P: probiotic (8.78 * 108 CFU/kg/day); (3) DEHP: 50 mg/kg b.w./day, (4) DBP: 50 mg/kg b.w./day, (5) BPA: 25 mg/kg b.w./day; (6) MIX: DEHP + DBP + BPA; (7) MIX + P. Lungs, thymus and kidneys were extracted and prepared for redox status and essential metals analysis. By conducting additional in vitro experiment, probiotic phthalate and BPA binding ability was explored. There were 24 DEHP, DBP and BPA asthma-related genes, indicating the three most probable mechanisms - apoptosis, inflammation and oxidative stress. In vivo experiment confirmed that significant changes in redox status/essential metal parameters were either prominent, or only present in the MIX group, indicating possible additive effects. In vitro experiment confirmed the ability of the multy-strain probiotic to bind DEHP/DBP/BPA mixture, while probiotic administration ameliorated mixture-induced changes in rat tissue. [Display omitted] •MIX (DEHP + DBP + BPA): 24 mutual genes connected with asthma development.•Apoptosis, inflammation and oxidative stress – the most probable mechanisms.•Redox status and bioelements changes – most prominent/present only in the MIX group.•Multi-strain probiotic bound 29.25, 29.04 and 41.75% for DEHP, DBP and BPA.•Probiotic mitigated MIX-induced changes in rat lung, thymus and kidney tissue.