Sobolewski Marissa, Allen Joshua L, Morris-Schaffer Keith, Klocke Carolyn, Conrad Katherine, Cory-Slechta Deborah A
Department of Environmental Medicine, University of Rochester, 575 Elmwood Ave, Box EHSC, Rochester, NY 14642, United States.
Neurotoxicol Teratol. 2016 Jul-Aug;56:75-80. doi: 10.1016/j.ntt.2016.04.002. Epub 2016 Apr 14.
Prenatal stress and nutrition are well-known to alter a broad range of physiological systems, notably metabolic, endocrine and neurobehavioral function. Commonly used methods for oral administration of xenobiotics can, by acting as a stressor or altering normal nutrition intake, alter these physiological systems as well. Taken together, oral administration methods may unintentionally introduce confounding physiological effects that can mask or enhance toxicity of xenobiotics, particularly if they share biological targets. Consequently, it should be preferable to develop alternative methods without these potential confounds. The aim of this study was to determine the suitability of mealworms as an alternative treat-based method to deliver xenobiotics via the orogastric route. Accurate oral administration is contingent on motivation and preference; mice reliably preferred mealworms over wafer cookie treats. Further, ingestion of wafer cookies significantly increased mouse blood glucose levels, whereas unaltered mealworms produced no such change. Mealworms functioned effectively to orally administer glucose, as glucose-spiked mealworms produced a rise in blood glucose equivalent to the ingestion of the wafer cookie. Mealworms did not interfere with the physiological function of orally administered d-amphetamine, as both mealworm and oral gavage administered d-amphetamine showed similar alterations in locomotor behavior (mice did not fully consume d-amphetamine-dosed cookies and thus could not be compared). Collectively, the findings indicate that mealworms are a preferred and readily consumed treat, which importantly mimics environmental-relevant nutritional intake, and mealworms per se do not alter glucose metabolic pathways. Additionally, mealworms accurately delivered xenobiotics into blood circulation and did not interfere with the physiological function of administered xenobiotics. Thus mealworm-based oral administration may be a preferable and accurate route of xenobiotic administration that eliminates physiological alterations associated with other methods of delivery.
众所周知，产前应激和营养会改变广泛的生理系统，尤其是代谢、内分泌和神经行为功能。常用的外源化合物口服给药方法，可能会作为一种应激源或改变正常营养摄入，进而也改变这些生理系统。综合来看，口服给药方法可能会无意中引入混淆的生理效应，从而掩盖或增强外源化合物的毒性，特别是当它们共享生物学靶点时。因此，开发没有这些潜在混淆因素的替代方法可能会更好。本研究的目的是确定黄粉虫作为一种基于食物的替代方法，通过口胃途径递送外源化合物的适用性。准确的口服给药取决于动机和偏好；小鼠确实更倾向于选择黄粉虫而非威化饼干。此外，摄入威化饼干会显著提高小鼠血糖水平，而未改变的黄粉虫则不会产生这种变化。黄粉虫能有效地口服递送葡萄糖，因为添加葡萄糖的黄粉虫使血糖升高，与摄入威化饼干相当。黄粉虫不会干扰口服给予的d - 苯丙胺的生理功能，因为黄粉虫给药和口服灌胃给予d - 苯丙胺在运动行为上显示出相似的变化（小鼠没有完全食用含d - 苯丙胺的饼干，因此无法进行比较）。总体而言，研究结果表明黄粉虫是一种首选且易于食用的食物，重要的是它模拟了与环境相关的营养摄入，并且黄粉虫本身不会改变葡萄糖代谢途径。此外，黄粉虫能准确地将外源化合物递送至血液循环，且不会干扰所给予外源化合物的生理功能。因此，基于黄粉虫的口服给药可能是一种更优且准确的外源化合物给药途径，可消除与其他给药方法相关的生理改变。
