Physiological Variation in Laboratory Animals and Humans

Various physiological factors influence the metabolic composition of the biofluids and tissues of living organisms. Both internal and external stimuli result in small metabolic adjustments in order to preserve homeostatic equilibrium in organisms. The metabolite profiles of the tissues and body fluids provide a fingerprint of the metabolic status of an animal and the expressed phenotype is a product of many genetic and environmental events. Factors such as diet, temperature, hydration state, hormonal cycles, metabolic rate, allostatic load, age, gender, and circadian rhythms all interact to influence the metabolism of an organism in a dynamic manner. In order to interpret and understand the metabolic consequences of pharmacology, pathology, or genetic modification, it is first necessary to define ʼnormality’ in healthy organisms and to establish the breadth of normal physiological variation. In general, pathological and toxicological effects on metabolite profiles are greater than pharmacological effects, with physiological variation causing even more subtle perturbations in comparison. Nevertheless, these subtle effects have a diverse range of both intrinsic and extrinsic sources, which affect many biochemical pathways resulting in characteristic metabolite variation in biofluids and tissues. These biochemical pathways may also be involved in toxification or detoxification of xenobiotics making it necessary to understand their contribution to defining 'ʼnormality’'.