title: Source of a micro-nutrient in a semi-synthetic basal diet as a causative factor in inducing urinary calculi in rats and its inhibition by PSC 833, a potent inhibitor of P-glycoprotein.
abstract: 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.
authors.affiliation: Department of Laboratory Medicine & Pathobiology, University of Toronto, Banting Institute, 100 College Street, Toronto, ON, Canada, M5G 1L5.
authors.forename: Janarthanan
authors.initials: J
authors.lastname: Kankesan
authors.forename: Ramesh
authors.initials: R
authors.lastname: Vanama
authors.forename: Richard
authors.initials: R
authors.lastname: Renlund
authors.forename: Jake J
authors.initials: JJ
authors.lastname: Thiessen
authors.forename: Victor
authors.initials: V
authors.lastname: Ling
authors.forename: Prema M
authors.initials: PM
authors.lastname: Rao
authors.forename: Srinivasan
authors.initials: S
authors.lastname: Rajalakshmi
authors.forename: Dittakavi S R
authors.initials: DS
authors.lastname: Sarma
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors*; D000818:Animals; D002794:Choline / Q000008:administration & dosage / Q000009:adverse effects; D003524:Cyclosporins / Q000008:administration & dosage*; D005260:Female; D005526:Food, Formulated / Q000009:adverse effects*; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley; D012376:Rodent Diseases / Q000209:etiology* / Q000517:prevention & control*; D013047:Specific Pathogen-Free Organisms; D014545:Urinary Calculi / Q000209:etiology / Q000517:prevention & control / Q000662:veterinary*
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D003524:Cyclosporins; D002794:Choline; C070272:valspodar