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Show COLLEGE OF SCIENCE Tessa Gotland Wayne Potts AN APPLICATION OF THE ORGANSIMAL PERFORMANCE ASSAY: TESTING THE SAFETY OF CERIVASTATIN Tessa Galland (Wayne Potts, Shannon Gaukler) Department of Biology University of Utah Before pharmaceuticals are deemed acceptable for study and use in h u m a n patients, they must pass through extensive testing on animal models. Nonetheless, even after extensive testing in animals, many of these drugs are found to produce serious adverse effects in h u m a n populations. Cerivastatin (Baycol), Rofecoxib (Vioxx), and Paroxetine (Paxil), for example, are just a few of the drugs that were found to produce serious negative effects in human populations after spending time on the market. Therefore, there is a great need for improved preclinical testing methodology that would detect the adverse effects of pharmaceuticals before they reach human patients. A novel drug research methodology, the Organismal Performance Assay (OPA) is conclusive, sensitive and applies evolutionary principles to rigorously test all components of physiological functioning simultaneously. It relies on genetically diverse populations of the model organism, M u s Musculus. In the OPA, individuals exposed to the pharmaceutical compete with individuals not exposed to the pharmaceutical for access to mates and territory within competitive semi-natural settings. Since these conditions are highly competitive, any decrease in physiological function can produce decreases in performance in multiple measures of evolutionary fitness; therefore, the fitness indicators of survivorship, reproductive success, and male territoriality are used to determine whether exposure to the drug produces adverse effects. The OPA has been applied to testing multiple pharmaceuticals. Recently it has been used to test the effects of exposure to the pharmaceutical, Cerivastatin, used to treat high cholesterol. Cerivastatin-exposed males had reduced performance by several measures. These males were significantly less dominant (p=0.0293), experienced significantly higher mortality (p=0.0350) and had significantly fewer sons (p=0.0159), than control males. Similarly, Cerivastatin-exposed females had a decreased reproductive success (p=0.0839), though w e still have one population to analyze. In contrast, mortality rate did not differ between Cerivastatin-exposed and control females.These results indicate that Cerivastatin m a y be detrimental to human health. Additionally, they confirm that the O P A could contribute useful information in pharmaceutical testing. |