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When investigating injury mechanisms and testing potential therapeutic interventions, it is therefore important to be mindful of the experimental design that could influence results including use of the most appropriate species and strains, optimal doses of APAP, the best experimental conditions (fasted vs fed, etc.), awareness that any treatment or interventions can have off-target effects including effects on the drug metabolism and antioxidant defense systems and be cognizant of the fact that genetic manipulations can trigger adaptive responses that also influence the outcome