Effects of different diuretics on tetracycline-induced hyperuraemia and hypercreatininaemia in the rat

Tetracycline injection (45 mg/kg, i.v.) produced increases in plasma urea and creatinine levels in rats. The greatest increases occurred after 24 hr for urea and after 6 hr for creatinine, the latter effect persisted for at least 30 hr. The actions of six diuretics (acetazolamide, bumetanide, chlorothiazide, chlorthalidone, triamterene and indapamide) given orally either as pretreatment (1 hr before tetracycline injection) or post-treatment (4 hr after tetracycline injection) were examined. When given as pretreatments, all six diuretics reduced the hyperuraemia, and generally the hypercreatininaemia, that existed 24 hr after tetracycline injection. In contrast, when given as post-treatments, only bumetanide reduced the increase in urea and creatinine levels. It is postulated that this protective action of diuretics could occur by their displacement of tetracycline molecules from protein binding sites or by a-direct action on renal function.