Wolkowski-Tyl R, Chin T Y
Fundam Appl Toxicol. 1983 Nov-Dec;3(6):552-8. doi: 10.1016/s0272-0590(83)80103-1.
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.
将雄性断乳Fischer 344大鼠在出生后第28 - 42天期间，用饮食中含4.0%对苯二甲酸（TPA）的饲料喂养两周（阳性对照），结果膀胱结石发病率达50%，出现酸尿、尿钙（Ca）和镁（Mg）排泄增加，且相对于阴性对照，血清Ca和Mg水平略有升高。在接触含4.0% TPA的饮食期间，通过每日口服推荐治疗剂量的别嘌呤醇、氯噻嗪或中性磷酸盐，研究TPA诱导尿路结石的可能机制。另一组大鼠在饮食中摄入4.0% TPA和4.0%碳酸氢钠，持续两周。氯噻嗪或饮食中的碳酸氢钠消除了TPA诱导的尿路结石，但别嘌呤醇和中性磷酸盐无效。碳酸氢钠使饮水量高于阳性对照，并改善了TPA诱导的酸尿。它还使尿Mg和TPA高于阳性对照值。氯噻嗪使尿Ca和TPA水平低于阳性对照。用氯噻嗪、中性磷酸盐或碳酸氢钠治疗使血清Ca略低于阳性或阴性对照水平。药物治疗未改变TPA诱导的血清Mg水平升高，但碳酸氢钠使血清Mg水平降至阴性对照值。总之，降低尿Ca和TPA排泄的治疗药物（氯噻嗪），或增加饮水量、尿Mg和TPA排泄并改善TPA诱导酸尿的药物（饮食中的碳酸氢钠），消除了雄性断乳大鼠中TPA诱导的尿路结石。这些因素似乎对TPA诱导的尿路结石至关重要。
