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. 1982 Sep;22(3):508–512. doi: 10.1128/aac.22.3.508

Reduction of experimental gentamicin nephrotoxicity in rats by dietary calcium loading.

W M Bennett, W C Elliott, D C Houghton, D N Gilbert, J DeFehr, D A McCarron
PMCID: PMC183773  PMID: 7137986

Abstract

Since gentamicin accumulates in the renal cortex before renal failure and calcium reduces gentamicin binding to cell membranes, we examined the effect of dietary calcium loading on gentamicin toxicity in male F344 rats. Rats were fed either a normal (0.5%)- or a high (4%)-calcium-content chow. Calcium loading did not alter inulin clearance, urinary excretion of sodium or total osmoles, or serum ionized calcium. However, calcium loading caused elevation of urinary calcium excretion and lowered urinary cyclic AMP levels. The data suggest that calcium loading may have slowed the accumulation of gentamicin (40 mg/kg per day) by the renal cortex. Histological and functional evidence of nephrotoxicity was delayed in onset and attenuated in magnitude. The results indicate that dietary calcium loading reduces experimental gentamicin nephrotoxicity. Protection may be associated with slower renal cortical accumulation of gentamicin. Calcium-dependent membrane or intracellular events may mediate this effect.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Adams H. R., Durrett L. R. Gentamicin blockade of slow Ca++ channels in atrial myocardium of guinea pigs. J Clin Invest. 1978 Aug;62(2):241–247. doi: 10.1172/JCI109122. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Agus Z. S., Puschett J. B., Senesky D., Goldberg M. Mode of action of parathyroid hormone and cyclic adenosine 3',5'-monophosphate on renal tubular phosphate reabsorption in the dog. J Clin Invest. 1971 Mar;50(3):617–626. doi: 10.1172/JCI106532. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bennett W. M., Hartnett M. N., Gilbert D., Houghton D., Porter G. A. Effect of sodium intake on gentamicin nephrotoxicity in the rat. Proc Soc Exp Biol Med. 1976 Apr;151(4):736–738. doi: 10.3181/00379727-151-39296. [DOI] [PubMed] [Google Scholar]
  4. Bennett W. M., Plamp C. E., 3rd, Parker R. A., Gilbert D. N., Houghton D. C., Porter G. A. Alterations in organic ion transport induced by gentamicin nephrotoxicity in the rat. J Lab Clin Med. 1980 Jan;95(1):32–39. [PubMed] [Google Scholar]
  5. Borle A. B. Calcium metabolism at the cellular level. Fed Proc. 1973 Sep;32(9):1944–1950. [PubMed] [Google Scholar]
  6. Bryan L. E., Van Den Elzen H. M. Effects of membrane-energy mutations and cations on streptomycin and gentamicin accumulation by bacteria: a model for entry of streptomycin and gentamicin in susceptible and resistant bacteria. Antimicrob Agents Chemother. 1977 Aug;12(2):163–177. doi: 10.1128/aac.12.2.163. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Dornbusch K. Influence of medium composition on bacterial susceptibility testing to gentamicin and netilmicin. Scand J Infect Dis Suppl. 1980;Suppl 23:46–53. [PubMed] [Google Scholar]
  8. Elliott W. C., Parker R. A., Houghton D. C., Gilbert D. N., Porter G. A., DeFehr J., Bennett W. M. Effect of sodium bicarbonate and ammonium chloride ingestion in experimental gentamicin nephrotoxicity in rats. Res Commun Chem Pathol Pharmacol. 1980 Jun;28(3):483–495. [PubMed] [Google Scholar]
  9. Gilbert D. N., Houghton D. C., Bennett W. M., Plamp C. E., Reger K., Porter G. A. Reversibility of gentamicin nephrotoxicity in rats: recovery during continuous drug administration. Proc Soc Exp Biol Med. 1979 Jan;160(1):99–103. doi: 10.3181/00379727-160-40397. [DOI] [PubMed] [Google Scholar]
  10. Goodman F. R. Distribution of 14C-gentamicin in vascular smooth muscle. Pharmacology. 1978;16(1):17–25. doi: 10.1159/000136741. [DOI] [PubMed] [Google Scholar]
  11. HAUGEN H. N. The determination of endogenous creatinine in plasma and urine. Scand J Clin Lab Invest. 1953;5(1):48–57. doi: 10.3109/00365515309093511. [DOI] [PubMed] [Google Scholar]
  12. Houghton D. C., Hartnett M., Campbell-Boswell M., Porter G., Bennett W. A light and electron microscopic analysis of gentamicin nephrotoxicity in rats. Am J Pathol. 1976 Mar;82(3):589–612. [PMC free article] [PubMed] [Google Scholar]
  13. Ichikawa I., Humes H. D., Dousa T. P., Brenner B. M. Influence of parathyroid hormone on glomerular ultrafiltration in the rat. Am J Physiol. 1978 May;234(5):F393–F401. doi: 10.1152/ajprenal.1978.234.5.F393. [DOI] [PubMed] [Google Scholar]
  14. Kornguth M. L., Bayer W. H., Kunin C. M. Binding of gentamicin to subcellular fractions of rabbit kidney: inhibition by spermine and other polyamines. J Antimicrob Chemother. 1980 Jan;6(1):121–131. doi: 10.1093/jac/6.1.121. [DOI] [PubMed] [Google Scholar]
  15. Morin J. P., Viotte G., Vandewalle A., Van Hoof F., Tulkens P., Fillastre J. P. Gentamicin-induced nephrotoxicity: a cell biology approach. Kidney Int. 1980 Nov;18(5):583–590. doi: 10.1038/ki.1980.176. [DOI] [PubMed] [Google Scholar]
  16. Myers D. R., DeFehr J., Bennet W. M., Porter G. A., Olsen G. D. Gentamicin binding to serum and plasma proteins. Clin Pharmacol Ther. 1978 Mar;23(3):356–360. doi: 10.1002/cpt1978233356. [DOI] [PubMed] [Google Scholar]
  17. Paradelis A. G., Triantaphyllidis C., Giala M. M. Neuromuscular blocking activity of aminoglycoside antibiotics. Methods Find Exp Clin Pharmacol. 1980 Feb;2(1):45–51. [PubMed] [Google Scholar]
  18. Racker E. Fluxes of Ca2+ and concepts. Fed Proc. 1980 May 15;39(7):2422–2426. [PubMed] [Google Scholar]
  19. Rasmussen H. Calcium and cAMP in stimulus-response coupling. Ann N Y Acad Sci. 1980;356:346–353. doi: 10.1111/j.1749-6632.1980.tb29622.x. [DOI] [PubMed] [Google Scholar]
  20. Schor N., Ichikawa I., Rennke H. G., Troy J. L., Brenner B. M. Pathophysiology of altered glomerular function in aminoglycoside-treated rats. Kidney Int. 1981 Feb;19(2):288–296. doi: 10.1038/ki.1981.19. [DOI] [PubMed] [Google Scholar]
  21. Simmons C. F., Jr, Bogusky R. T., Humes H. D. Inhibitory effects of gentamicin on renal mitochondrial oxidative phosphorylation. J Pharmacol Exp Ther. 1980 Sep;214(3):709–715. [PubMed] [Google Scholar]

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