Effects of selected therapeutic agents on urolithiasis induced by terephthalic acid in the male weanling Fischer 344 rat.
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.
D000493:Allopurinol / Q000627:therapeutic use; D000818:Animals; D001639:Bicarbonates / Q000627:therapeutic use; D002118:Calcium / Q000097:blood; D002740:Chlorothiazide / Q000627:therapeutic use; D004435:Eating / Q000187:drug effects; D008274:Magnesium / Q000652:urine; D008297:Male; D010710:Phosphates / Q000627:therapeutic use; D010795:Phthalic Acids / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344; D001744:Urinary Bladder Calculi / Q000139:chemically induced / Q000188:drug therapy*
D001639:Bicarbonates; D010710:Phosphates; D010795:Phthalic Acids; D000493:Allopurinol; C011363:terephthalic acid; D002740:Chlorothiazide; D008274:Magnesium; D002118:Calcium