Dynamic model of eicosanoid production with special reference to non‐steroidal anti‐inflammatory drug‐triggered hypersensitivity
| Autor: | Tadej Emeršič, Dirk Schäfer, Aleš Fajmut, Milan Brumen, Nataša Antić, Andrej Dobovišek |
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| Rok vydání: | 2015 |
| Předmět: |
musculoskeletal diseases
Population Inflammation Pharmacology Biology Drug Hypersensitivity chemistry.chemical_compound Genetics medicine Humans Computer Simulation education Molecular Biology Research Articles chemistry.chemical_classification education.field_of_study Aspirin Anti-Inflammatory Agents Non-Steroidal Models Immunological Computational Biology Cell Biology Kinetics Metabolic pathway Enzyme chemistry Modeling and Simulation Immunology Eicosanoids lipids (amino acids peptides and proteins) Bronchoconstriction Arachidonic acid medicine.symptom Biotechnology medicine.drug Eicosanoid Production |
| Zdroj: | IET Syst Biol |
| ISSN: | 1751-8857 1751-8849 |
| DOI: | 10.1049/iet-syb.2014.0037 |
| Popis: | The authors developed a mathematical model of arachidonic acid (AA) degradation to prostaglandins (PGs) and leukotrienes (LTs), which are implicated in the processes of inflammation and hypersensitivity to non‐steroidal anti‐inflammatory drugs (NSAIDs). The model focuses on two PGs (PGE(2) and PGD(2)) and one LT (LTC(4)), their % increases and their ratios. Results are compared with experimental studies obtained from non‐asthmatics (NAs), and asthmatics tolerant (ATA) or intolerant (AIA) to aspirin. Simulations are carried out for predefined model populations NA, ATA and three AIA, based on the differences of two enzymes, PG E synthase and/or LTC(4)‐synthase in two states, that is, no‐inflammation and inflammation. Their model reveals that the model population with concomitant malfunctions in both enzymes is the most sensitive to NSAIDs, since the duration and the capacity for bronchoconstriction risk are highest after simulated oral dosing of indomethacin. Furthermore, inflammation prolongs the duration of the bronchoconstriction risk in all AIA model populations, and the sensitivity analysis reveals multiple possible scenarios leading to hypersensitivity, especially if inflammatory processes affect the expression of multiple enzymes of the AA metabolic pathway. Their model estimates the expected fold‐changes in enzyme activities and gives valuable information for further targeted transcriptomic/proteomic and metabolomic studies. |
| Databáze: | OpenAIRE |
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