Urolithiasis in Rats Consuming a dl Bitartrate Form of Choline in a Purified Diet
Abstract:Urolithiasis appeared in rats maintained to study the effects of nutrients and methylmercury on development and aging. After a year, the mortality rate was approximately 10%, and by 2 years, it had increased to nearly 30%. Clinical signs and urinary tract pathology were examined as a function of diet, duration on diet, gender, methylmercury exposure, genetics, and other potential risk factors by using survival analyses and qualitative comparisons. Urolithiasis in female rats appeared 15 weeks after beginning a purified diet and after 5 weeks for male rats. After 97 weeks, the mortality rate of female rats was 22% and for male rats was 64%. Lifetime urolithiasis-associated mortality was about 2% in a group of rats that consumed the contaminated diet for < 30 weeks. No urolithiasis occurred in siblings or cohorts of the rats described here that were maintained on a standard rodent chow containing choline chloride. Urolithiasis was traced to racemic, rather than levo-, bitartaric acid in some purified diets shipped in 2001 and 2002. It is unknown when the impurity first appeared in the diet, so estimates of exposure duration are upper limits. Chronic methylmercury exposure increased vulnerability. Some families (dam + offspring) had multiple cases of urolithiasis, but probability models constructed to evaluate familial clustering revealed no evidence for a genetic predisposition to urolithiasis apart from gender. Removing racemic tartaric acid did not decrease mortality once rats had been on the diet for 20 to 30 weeks, but it helped when exposure duration was shorter.
Document Type: Research Article
Affiliations: 1: Behavioral Toxicology Laboratory, Experimental Psychology, 226 Thach, Auburn University, Alabama 36849 2: Department of Psychology, Alabama State University, Montgomery, Alabama 36101 3: Department of Pathobiology, 166 Greene Hall, College of Veterinary Medicine, Auburn University, Alabama 36849 4: Laboratory Animal Health, 311 Greene Hall Annex, College of Veterinary Medicine, Auburn University, Alabama 36849 5: Department of Nutrition and Food Science, 328 Spidle Hall, Auburn University, Alabama 36849 6: Department of Medicine/Research Service, Medical College of Wisconsin/Zablocki VA Medical Center, 5000 W. National Avenue, Milwaukee, Wisconsin 53295
Publication date: August 1, 2005
Comparative Medicine (CM), an international journal of comparative and experimental medicine, is the leading English-language publication in the field and is ranked by the Science Citation Index in the upper third of all scientific journals. The mission of CM is to disseminate high-quality, peer-reviewed information that expands biomedical knowledge and promotes human and animal health through the study of laboratory animal disease, animal models of disease, and basic biologic mechanisms related to disease in people and animals.
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