Damsch Siegrid, Eichenbaum Gary, Tonelli Alfred, Lammens Lieve, Van den Bulck Kathleen, Feyen Bianca, Vandenberghe John, Megens Anton, Knight Elaine, Kelley Michael
Johnson & Johnson Pharmaceutical Research and Development, Beerse, Belgium.
Toxicol Pathol. 2011 Feb;39(2):348-60. doi: 10.1177/0192623310388431. Epub 2010 Dec 14.
After oral gavage dosing of rats, reflux may occur, resulting in serious respiratory effects and mortality. Published information on gavage-related reflux is limited, as it has not yet been a focus of research. Nevertheless, it represents a recurrent challenge in daily toxicology practice of oral gavage dosing. The absence of clear guidance and criteria for the identification and management of reflux-induced effects can limit the ability to properly interpret toxicity study results. The review presented herein includes an overview of experimental data from gavage studies in rats, in which reflux was observed, and provides a comprehensive analysis of the literature on reflux in general and the different potential pathways contributing to gavage-related reflux in rats. The article aims to increase the awareness and understanding of the pathogenesis of gavage-related reflux and provides guidance on identification of potential risk factors, as well as interpretation of histological changes and their toxicological relevance. Furthermore, differentiation of reflux-induced effects from direct compound-related toxicity and from gavage errors is addressed in particular, and the importance of nasal histology is discussed.
给大鼠经口灌胃给药后，可能会发生反流，从而导致严重的呼吸道影响和死亡。关于灌胃相关反流的已发表信息有限，因为它尚未成为研究重点。然而，在每日经口灌胃给药的毒理学实践中，这是一个反复出现的挑战。缺乏关于反流所致影响的识别和管理的明确指南及标准，可能会限制正确解读毒性研究结果的能力。本文所呈现的综述包括对大鼠灌胃研究中观察到反流的实验数据的概述，并对一般反流以及导致大鼠灌胃相关反流的不同潜在途径的文献进行了全面分析。本文旨在提高对灌胃相关反流发病机制的认识和理解，并提供关于潜在风险因素识别、组织学变化解读及其毒理学相关性的指导。此外，特别讨论了如何区分反流所致影响与直接的化合物相关毒性以及灌胃失误，并探讨了鼻腔组织学的重要性。
