Melanie R Warren1, Andreea Radulescu2, Peter Dornbos3, Danila Cuomo2, Shelby Zumwalt2, Diana Bueso-Mendoza2, Megan Nitcher2, John J LaPres3, David W Threadgill4. 1. Interdisciplinary Faculty of Toxicology, Texas A&M College of Veterinary Medicine & Biomedical Sciences, College Station, TX, USA; Department of Molecular and Cellular Medicine, Texas A&M College of Medicine, College Station, TX, USA. 2. Department of Molecular and Cellular Medicine, Texas A&M College of Medicine, College Station, TX, USA. 3. Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI, USA; Institute for Integrative Toxicology, Michigan State University, East Lansing, MI, USA. 4. Interdisciplinary Faculty of Toxicology, Texas A&M College of Veterinary Medicine & Biomedical Sciences, College Station, TX, USA; Department of Molecular and Cellular Medicine, Texas A&M College of Medicine, College Station, TX, USA; Department of Biochemistry and Biophysics, Texas A&M University, College Station, TX, United States of America. Electronic address: dwt@tamu.edu.
Abstract
INTRODUCTION: Animal-based studies are essential for assessing toxicity to environmental pollutants, especially when the potential targets are specific developmental time points, teratogenic, or multi-organ systems that cannot be modeled in vitro. Orogastric gavage is a widely used technique for exposure because of its increased accuracy of dose administration over free feeding. However, repeated use of this method has been reported to cause physiological stress on the exposed animals that could interfere with interpretation of results. Previous studies have shown that genetic background also contributes to the level of stress and can affect individual response. METHODS: To evaluate the impact of stress on repeated orogastric gavage, we exposed C67BL/6J and 129S1/SvImJ inbred mouse strains to 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD), a potent xenobiotic that has been extensively studied in vivo. Pregnant females were dosed for ten days after mating using orogastric gavage with olive oil as vehicle or through diet using peanut butter as vehicle. Serum corticosterone levels, body weight, and reproduction endpoints were measured to evaluate levels of stress induced by the dosing technique. RESULTS: The levels of stress caused by orogastric gavage was strongly dependent on strain background and on the phenotypic endpoint. Orogastric gavage-induced stress was more detrimental in 129S1/SvlmJ pregnant female mice than in C57BL/6J. CONCLUSION: These results show that administration of xenobiotics via controlled diet can improve the reproducibility and rigor of exposure studies requiring orogastric delivery.
INTRODUCTION: Animal-based studies are essential for assessing toxicity to environmental pollutants, especially when the potential targets are specific developmental time points, teratogenic, or multi-organ systems that cannot be modeled in vitro. Orogastric gavage is a widely used technique for exposure because of its increased accuracy of dose administration over free feeding. However, repeated use of this method has been reported to cause physiological stress on the exposed animals that could interfere with interpretation of results. Previous studies have shown that genetic background also contributes to the level of stress and can affect individual response. METHODS: To evaluate the impact of stress on repeated orogastric gavage, we exposed C67BL/6J and 129S1/SvImJ inbred mouse strains to 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD), a potent xenobiotic that has been extensively studied in vivo. Pregnant females were dosed for ten days after mating using orogastric gavage with olive oil as vehicle or through diet using peanut butter as vehicle. Serum corticosterone levels, body weight, and reproduction endpoints were measured to evaluate levels of stress induced by the dosing technique. RESULTS: The levels of stress caused by orogastric gavage was strongly dependent on strain background and on the phenotypic endpoint. Orogastric gavage-induced stress was more detrimental in 129S1/SvlmJ pregnant female mice than in C57BL/6J. CONCLUSION: These results show that administration of xenobiotics via controlled diet can improve the reproducibility and rigor of exposure studies requiring orogastric delivery.
Authors: I M Kapetanovic; R Krishnaraj; T Martin-Jimenez; L Yuan; R B van Breemen; A Lyubimov Journal: Chem Biol Interact Date: 2006-09-01 Impact factor: 5.192
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