Kankesan Janarthanan, Vanama Ramesh, Renlund Richard, Thiessen Jake J, Ling Victor, Rao Prema M, Rajalakshmi Srinivasan, Sarma Dittakavi S R
Department of Laboratory Medicine & Pathobiology, University of Toronto, Banting Institute, 100 College Street, Toronto, ON, Canada, M5G 1L5.
Comp Med. 2003 Aug;53(4):444-7.
We report a serendipitous finding of urinary calculi in rats fed a semi-synthetic basal diet. This observation was made during ongoing studies to evaluate the inhibitory effect of PSC 833, a potent inhibitor of P-glycoprotein, on development of tumors in rodent tumor model systems. A large number of specific-pathogen-free (SPF) female Sprague-Dawley and SPF male Fischer 344 rats being fed the diet were euthanized when it became evident clinically that they were uremic. At necropsy, the renal pelvis, ureters, and urinary bladder contained numerous calculi. The presence of urinary calculi was determined to be related to the source of a Food Chemical Codex grade of choline bitartrate. Rats being fed the same basal diet containing the United States Pharmacopia grade of choline bitartrate failed to develop urinary calculi. Interestingly, rats treated with the P-glycoprotein inhibitor were at significantly reduced risk of developing urinary calculi. This finding highlights how something seemingly innocuous as a minor dietary constituent can have a profound impact and, thereby, affect experimental outcome.
我们报告了一个在喂食半合成基础饮食的大鼠中意外发现尿路结石的情况。这一观察结果是在正在进行的研究中得出的，该研究旨在评估P-糖蛋白的强效抑制剂PSC 833对啮齿动物肿瘤模型系统中肿瘤发展的抑制作用。当喂食该饮食的大量无特定病原体（SPF）雌性斯普拉格-道利大鼠和SPF雄性费希尔344大鼠临床上明显出现尿毒症时，将它们安乐死。尸检时，肾盂、输尿管和膀胱中含有大量结石。尿路结石的出现被确定与食品化学法典级酒石酸胆碱的来源有关。喂食含有美国药典级酒石酸胆碱的相同基础饮食的大鼠未出现尿路结石。有趣的是，用P-糖蛋白抑制剂治疗的大鼠患尿路结石的风险显著降低。这一发现凸显了一种看似无害的微量饮食成分如何能产生深远影响，从而影响实验结果。
