Kazuhiro Terai1, Kazuhiko Mizukami, Masamichi Okada. 1. Kidney and Digestive Tracts Laboratory, Institute of Pharmacology, Astellas Pharma Co. Ltd, Miyukigaoka, Tsukuba, Ibaraki, Japan. kazuhiro.terai@jp.astellas.com
Abstract
BACKGROUND: Several animal models with chronic renal failure have been established and used for demonstrating complications including hyperphosphataemia. Although long-time feeding is required to cause hyperphosphataemia in animals, a few modifications have been reported to provide more useful models for research. METHODS: Three separate experiments were carried out in the present study. First, characteristics of commonly used subnephrectomized (5/6Nx) rats and rats fed an adenine diet (0.75% adenine in normal diet) were compared as hyperphosphataemia models. Next, using adenine-diet rats, the inhibitory effect of sevelamer hydrochloride (Sev) on serum phosphorus elevation was examined. Third, oral adenine dosing for induction of hyperphosphataemia and validation as a model using Sev were examined. RESULTS: Serum phosphorus in 5/6Nx rats became elevated in 8-17 weeks, but the levels and time points of elevation differed among animals. In adenine-fed rats, the elevation was more clearly demonstrated with less diversity at 4 weeks. The data revealed a potential shorter model preparation period and the importance of controlling feeding amounts. Oral adenine dosing induced hyperphosphataemia by 12 days, and Sev treatment was inhibitory. After a maintenance period of over a month (no treatments), Sev-treated rats showed hyperphosphataemia as did oral adenine-dosed control rats. The serum phosphorus levels significantly decreased on further Sev treatment. CONCLUSION: Oral dosing with adenine made the model preparation period definitely shorter, and its usefulness as a hyperphosphataemia model was revealed using Sev.
BACKGROUND: Several animal models with chronic renal failure have been established and used for demonstrating complications including hyperphosphataemia. Although long-time feeding is required to cause hyperphosphataemia in animals, a few modifications have been reported to provide more useful models for research. METHODS: Three separate experiments were carried out in the present study. First, characteristics of commonly used subnephrectomized (5/6Nx) rats and rats fed an adenine diet (0.75% adenine in normal diet) were compared as hyperphosphataemia models. Next, using adenine-diet rats, the inhibitory effect of sevelamer hydrochloride (Sev) on serum phosphorus elevation was examined. Third, oral adenine dosing for induction of hyperphosphataemia and validation as a model using Sev were examined. RESULTS: Serum phosphorus in 5/6Nx rats became elevated in 8-17 weeks, but the levels and time points of elevation differed among animals. In adenine-fed rats, the elevation was more clearly demonstrated with less diversity at 4 weeks. The data revealed a potential shorter model preparation period and the importance of controlling feeding amounts. Oral adenine dosing induced hyperphosphataemia by 12 days, and Sev treatment was inhibitory. After a maintenance period of over a month (no treatments), Sev-treated rats showed hyperphosphataemia as did oral adenine-dosed control rats. The serum phosphorus levels significantly decreased on further Sev treatment. CONCLUSION: Oral dosing with adenine made the model preparation period definitely shorter, and its usefulness as a hyperphosphataemia model was revealed using Sev.
Authors: Bo Wang; Radko Komers; Rosemarie Carew; Catherine E Winbanks; Bei Xu; Michal Herman-Edelstein; Philip Koh; Merlin Thomas; Karin Jandeleit-Dahm; Paul Gregorevic; Mark E Cooper; Phillip Kantharidis Journal: J Am Soc Nephrol Date: 2011-11-17 Impact factor: 10.121
Authors: K Terai; H Nara; K Takakura; K Mizukami; M Sanagi; S Fukushima; A Fujimori; H Itoh; M Okada Journal: Br J Pharmacol Date: 2009-03-19 Impact factor: 8.739
Authors: Bo Wang; Philip Koh; Catherine Winbanks; Melinda T Coughlan; Aaron McClelland; Anna Watson; Karin Jandeleit-Dahm; Wendy C Burns; Merlin C Thomas; Mark E Cooper; Phillip Kantharidis Journal: Diabetes Date: 2010-10-15 Impact factor: 9.461
Authors: Ai-Ching Boon; Alfred K Lam; Vinod Gopalan; Iris F Benzie; David Briskey; Jeff S Coombes; Robert G Fassett; Andrew C Bulmer Journal: Sci Rep Date: 2015-10-26 Impact factor: 4.379
Authors: Guaraciaba O Ferrari; Juliana C Ferreira; Raquel T Cavallari; Katia R Neves; Luciene M dos Reis; Wagner V Dominguez; Elizabeth C Oliveira; Fabiana G Graciolli; Jutta Passlick-Deetjen; Vanda Jorgetti; Rosa M A Moysés Journal: BMC Nephrol Date: 2014-05-03 Impact factor: 2.388