The rapid establishment and implications of a melamine-induced standardized bladder stone model in mice.

Abstract

The key to establishing a standardized melamine-induced animal bladder stone (cystolith) model is to determine the most appropriate daily dose of dietary melamine, which is unknown. Based on golden section theory that is a well-known preferred proportion (0.618), and the 50% lethal dose (LD50) of mouse oral melamine [4550 mg/kg body weight (bw)], we proposed that the daily dose may be close to the LD50's golden section (i.e., 0.618 × 4550 mg melamine/kg bw). The latter as an average daily dose corresponds to 9373 ppm melamine diet in mice. In repeated experiments, a 100% incidence of cystoliths was observed on modeling day 14 in Balb/c and C57BL/6 mice fed the diet but not in mice fed similar diets containing 9842 (i.e., 9373 × 105%) or 8904 (i.e., 9373 × 95%) ppm melamine; the stones were relatively uniform and the difference in stone incidences between sexes or ages was not found in each 9373 ppm melamine group. In conclusion, 9373 ppm melamine diet is at least near the optimal dose diet or ideal for the rapid and stable establishment of a standardized cystolith model in the mice, and dietary melamine dose neither sex nor age is critical for stone formation.