ABSTRACT
The use of the miniature swine as a nonrodent species in research has continued to expand for over a decade, and they are becoming routinely used both in experimental pharmacology and as a therapeutic model for human diseases. Miniature swine models are regularly used for studies designed to assess efficacy and safety of new therapeutic compounds given through different routes of exposure and are used as an alternative model to rodents, canines, or nonhuman primates. Translational preclinical swine study data presented here support the current understanding that miniature swine are the animal model of choice for the assessment of drugs targeting endocrine, dermal, and ocular disorders. Because research investigators need to be familiar with some of the important features of the models developed in the miniature swine in order to place clinical and experimental findings in their proper perspective, relevant references and data from these models will be presented, compared, and partially illustrated.
Subject(s)
Disease Models, Animal , Swine, Miniature , Translational Research, Biomedical/methods , Animals , Humans , SwineABSTRACT
The use of miniature swine as a nonrodent species in safety assessment has continued to expand for over a decade, and they are becoming routinely used in toxicology and in pharmacology as well as a model for human diseases. Miniature swine models are regularly used for regulatory toxicity studies designed to assess safety of new therapeutic compounds given through different routes of exposure and are used as an alternative model to the canine or the nonhuman primate. Translational preclinical swine study data presented support the current finding that miniature swine are the animal model of choice for assessment of drug absorption, tolerance, and systemic toxicity following systemic exposures. Because research investigators need to be familiar with important anatomic and histopathologic features of the miniature swine in order to place toxicopathologic findings in their proper perspective, clinical and anatomic pathology data from a large number of Sinclair, Hanford, Yucatan, and Göttingen breeds from control groups from a wide variety of studies performed between 2004 and 2014 will be presented, compared, and partially illustrated.
Subject(s)
Drug Evaluation, Preclinical , Swine, Miniature/anatomy & histology , Swine, Miniature/physiology , Toxicity Tests , Animals , Female , Histocytochemistry , Male , Models, Animal , SwineABSTRACT
BACKGROUND/PURPOSE: This study determined the threshold doses for 'solar erythema' and for phototoxic responses to 8-methoxypsoralen (8-MOP) in white skin Hanford and grey skin Yucatan miniature swine. METHODS: For threshold erythema determinations, the UVR exposures included both UVA (315-400 nm) and UVB (290-315 nm) radiation by positioning one fluorescent 'sunlamp' among 10 'PUVA' lamps. With this configuration the UVR exposures ranged from 0.5-2.8 times the 'instrumental MED' (MEDi) for Hanford and from 1.0-5.6 times the MEDi for Yucatan. For phototoxicity determinations (i.e., with and without topically-applied graduated concentrations of 8-MOP), the UVB component was minimized by extinguishing the sunlamp, thus permitting higher UVA exposures. RESULTS: The Hanford had the lower UV erythema dose threshold (1.0-1.4 times the MEDi) and the erythema that developed was readily observable. The exposure doses for the phototoxicity test were 5 J/cm(2) of UVA in 35 minutes or 10 J/cm(2) in 70 minutes. The phototoxic (vascular) response to 8-MOP was observed in the two highest concentrations (0.01% and 0.1%) in Hanford pigs, in a dose-related manner. Microscopic evidence of a dose-related response was also observed as the concentration of 8-MOP increased. CONCLUSION: This verified that the Hanford miniature swine is the preferable strain for phototoxic effects. In contrast, UVR exposure of the Yucatan pig skin produced tanning rather than erythema, confirming that the Yucatan is the more appropriate strain for studying the melanization response. Thus, Hanford and Yucatan miniature swine have cutaneous photobiological responses that reflect their respective strain differences.
