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

Abstract

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.

• Authors: Katarina Baralić, Dragica Bozic, Katarina Živančević, Milan Milenković, Dragana Javorac, Đurđica Marić, Evica Antonijević Miljaković, Aleksandra Buha Djordjevic, Predrag Vukomanović, Marijana Ćurčić, Zorica Bulat, Biljana Antonijević, Danijela Đukić-Ćosić
• Journal: Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association (Food Chem Toxicol) Vol. 158 Pg. 112671 (Dec 2021) ISSN: 1873-6351 [Electronic] England
• PMID: 34793900 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 Elsevier Ltd. All rights reserved.

Chemical References

• Benzhydryl Compounds
• Endocrine Disruptors
• Phenols
• Phthalic Acids
• bisphenol A

Topics

• Animals
• Asthma (chemically induced)
• Benzhydryl Compounds (toxicity)
• Computer Simulation
• Endocrine Disruptors (toxicity)
• Humans
• Kidney (drug effects)
• Lung (drug effects)
• Male
• Oxidative Stress (drug effects)
• Phenols (toxicity)
• Phthalic Acids (toxicity)
• Probiotics (pharmacology)
• Rats
• Thymus Gland (drug effects)
• Toxicogenetics