PROTECTIVE EFFECT OF ASCORBIC ACID, ISOASCORBIC ACID AND MANNITOL AGAINST TETRACYCLINE-INDUCED NEPHROTOXICITY

¹ Division of Medical Research, Sloan-Kettering Institute for Cancer Research and Departments of Medicine, Memorial Hospital and Cornell University College, New York, New York

The marked azotemia and other evidence of renal damage induced in rats and dogs by rapid i.v. administration of pure tetracycline ^· HCl at 50 mg/kg was prevented by concomitant administration of ascorbic acid at 125 mg/kg or higher. d-Isoascorbic acid had a similar effect when tested in rats. Mannitol was protective in dogs but had no consistent benefit in rats. When injection of ascorbic acid into rats preceded that of tetracycline by 5 to 10 minutes, protection was marked; reversal of the order of injections with the same interval resulted in less protection. Ascorbic acid was ineffective against antibiotic toxicity when blood flow to rat kidneys was prevented by renal pedicle ligation. Ascorbic acid increased the rate of dialysis and the percentage of ultrafiltration of tritiated tetracycline from plasma. The protective effect of ascorbic acid, isoascorbic acid and mannitol (the latter in dogs) against the nephrotoxicity of tetracycline is postulated to be secondary to an osmotic diuretic effect. Decreased protein binding in the plasma by ascorbic acid may be a contributing factor.