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Research ArticleArticle

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

ROMAN B. POLEC, SAMUEL D. J. YEH and MAURICE E. SHILS
Journal of Pharmacology and Experimental Therapeutics July 1971, 178 (1) 152-158;
ROMAN B. POLEC
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SAMUEL D. J. YEH
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MAURICE E. SHILS
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Abstract

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.

Footnotes

    • Received September 10, 1970.
    • Accepted April 1, 1971.
  • © 1971, by The Williams & Wilkins Company

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Journal of Pharmacology and Experimental Therapeutics
Vol. 178, Issue 1
1 Jul 1971
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Research ArticleArticle

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

ROMAN B. POLEC, SAMUEL D. J. YEH and MAURICE E. SHILS
Journal of Pharmacology and Experimental Therapeutics July 1, 1971, 178 (1) 152-158;

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Research ArticleArticle

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

ROMAN B. POLEC, SAMUEL D. J. YEH and MAURICE E. SHILS
Journal of Pharmacology and Experimental Therapeutics July 1, 1971, 178 (1) 152-158;
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