Reducing the effects of drug toxicity on glutathione metabolism

摘要: Abstract Glutathione metabolism plays a crucial role in drug detoxification. Overdose of paracetamol depletes glutathione cells, leading to oxidative stress and covalent modification cellular macromolecules, eventually causing liver damage. Numerous factors influence the synthesis depletion glutathione, therefore development systems biology tools is critical understanding relationship between toxicity. Currently, most clinical drugs that treat diseases focus on only one target, high dosage single-target may increase risk In this study, we developed model-based approach determine optimal strategies for reducing effects toxicity metabolism, considering therapeutic effect minimum effective dose (MED) simultaneously. Quantitative analyses revealed at least two target enzymes are required achieve 100% recovery γ -glutamyl transpeptidase (GGT) key enzyme metabolism. Computational results also supported interventions multiple targets necessary, further validating importance combination approaches disease treatments.