Exposure of male weanling Fischer 344 rats to 4.0%
terephthalic acid (TPA) in the diet (positive controls) for two weeks (postnatal days 28-42) resulted in a 50% incidence of
bladder calculi, aciduria, elevated urinary excretion of
calcium (Ca) and
magnesium (Mg), and slightly elevated serum levels of Ca and Mg relative to negative controls. Possible mechanisms of TPA-induced
urolithiasis were examined by daily
oral administration of
allopurinol,
chlorothiazide, or neutral
phosphates, at their recommended therapeutic doses during exposure to dietary 4.0% TPA. An additional group was fed 4.0% TPA and 4.0%
sodium bicarbonate in the diet for two weeks.
Chlorothiazide or dietary
bicarbonate abolished TPA-induced
urolithiasis, but
allopurinol and neutral
phosphates had no effect.
Bicarbonate increased water intake above that of positive controls and ameliorated the TPA-induced aciduria. It also increased urinary Mg and TPA above positive control values.
Chlorothiazide reduced urinary Ca and TPA levels below those of positive controls. Treatment with
chlorothiazide, neutral
phosphates or
bicarbonate slightly reduced serum Ca below the levels in either positive or negative controls.
Drug treatment did not alter TPA-induced elevated serum Mg levels, but
bicarbonate reduced serum Mg levels to negative control values. In conclusion, TPA-induced
urolithiasis in male weanling rats was abolished by therapeutic agents which reduced urinary Ca and TPA excretion (
chlorothiazide), or which enhanced water intake, urinary Mg and TPA excretion, and ameliorated TPA-induced aciduria (dietary
bicarbonate). These factors appear to be critical for TPA-induced
urolithiasis.