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 Molecular and Cellular Medicine, Texas A&M College of Medicine, College Station, TX, USA.
J Pharmacol Toxicol Methods. 2021 Jan-Feb;107:106948. doi: 10.1016/j.vascn.2020.106948. Epub 2020 Dec 30.
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.
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.
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.
These results show that administration of xenobiotics via controlled diet can improve the reproducibility and rigor of exposure studies requiring orogastric delivery.
动物研究对于评估环境污染物的毒性至关重要，特别是当潜在目标是特定的发育时间点、致畸或多器官系统，无法在体外建模时。经口灌胃是一种广泛使用的暴露技术，因为它比自由喂养更能准确地给药剂量。然而，据报道，这种方法的重复使用会对暴露动物造成生理压力，从而干扰结果的解释。先前的研究表明，遗传背景也会导致应激水平，并可能影响个体反应。
为了评估应激对重复经口灌胃的影响，我们使 C67BL/6J 和 129S1/SvImJ 近交系小鼠暴露于 2,3,7,8-四氯二苯并对二恶英（TCDD）中，这是一种在体内被广泛研究的强效外来化合物。雌性在交配后通过经口灌胃用橄榄油作为载体或通过饮食用花生酱作为载体连续十天给药。测量血清皮质酮水平、体重和繁殖终点，以评估给药技术引起的应激水平。
经口灌胃引起的应激水平强烈依赖于品系背景和表型终点。129S1/SvlmJ 妊娠雌鼠经口灌胃引起的应激比 C57BL/6J 更为严重。
这些结果表明，通过控制饮食给予外源性化合物可以提高需要经口灌胃给药的暴露研究的重现性和严格性。
