Nephrotoxicity pp 457-461 | Cite as

The Role of Oxidative Stress in Cephaloridine Nephrotoxicity

  • Robin S. Goldstein
  • Randall S. Sozio
  • Joan B. Tarloff
  • Jerry B. Hook


The cephalosporin antibiotic, cephaloridine (CPH), is nephrotoxic when administered in large dosages to humans and laboratory animals (1,2) . In vivo, CPH nephrotoxicity is characterized histologically by acute proximal tubular necrosis and functionally by glycosuria, enzymuria, proteinuria and an impaired ability of renal cortical slices to accumulate organic ions (1-4). Previous studies have indicated that the nephrotoxicity of CPH is intimately related to its renal cortical accumulation and intracellular concentration (5). CPH is actively transported into the proximal tubule cell by an organic anion transport system (5,6). However, unlike many organic anions and cephalosporins, CPH undergoes only limited movement across the lumenal membrane into the tubular fluid. Consequently, high intracellular concentrations of CPH are attained in the proximal tubule which are critical to the development of nephrotoxicity (5).


Toxicity Thiol Catalase Proteinuria Hydroperoxide 
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  1. 1.
    R.M. Atkinson, J.P. Currie, B. Davis, D.A.H. Pratt, H.M. Sharpe, and E.G. Tomich, Acute toxicity of cephaloridine, an antibiotic derived from cephalosporin C, Toxicol. Appl. Pharmacol. 8:398 (1966).PubMedCrossRefGoogle Scholar
  2. 2.
    R.D. Foord, Cephaloridine, cephalothin and the kidney, J. Antimicrob. Chemother. Suppi. 1:119 (1975).CrossRefGoogle Scholar
  3. 3.
    J.S. Welles, W.R. Gibson, P.N. Harris, R.M. Small and R.C. Anderson, Toxicity, distribution and excretion of cephaloridine in laboratory animals, Antimicrob. Agents Chemother. 1965:863 (1965).Google Scholar
  4. 4.
    J.S. Wold, Cephalosporin Nephrotoxicity, In: “Toxicity of the Kidney”, J.B. Hook, ed., Raven Press, New York (1981).Google Scholar
  5. 5.
    B. Tune, Relationship between the transport and toxicity of cephalosporins in the kidney, J. Infect Pis. 132:189 (1975).CrossRefGoogle Scholar
  6. 6.
    K.J. Child and M.G. Dodds, Nephron transport and renal tubular effects of cephaloridine in animals, Brit. J. Pharmacol. Chemother. 30:354 (1967).CrossRefGoogle Scholar
  7. 7.
    C.-H. Kuo, K. Maita, S.D. Sleight and J.B. Hook, Lipid peroxidation: A possible mechanism of cephaloridine-induced nephrotoxicity, Toxicol. Appl. Pharmacol. 67:78 (1983).PubMedCrossRefGoogle Scholar
  8. 8.
    R.S. Goldstein, D.A. Pasino, W.R. Hewitt and J.B. Hook, Biochemical mechanisms of cephaloridine nephrotoxicity: time and concentration dependence of peroxidative injury, Toxicol. Appl. Pharmacol. 83:43 (1986).CrossRefGoogle Scholar
  9. 9.
    C. Cojocel, J. Hannemann and K. Baumann, Cephaloridine-induced lipid peroxidation initiated by reactive oxygen species as a possible mechanism of cephaloridine nephrotoxicity, Biochem. Biophvs. Acta 834:402 (1985).CrossRefGoogle Scholar
  10. 10.
    D. DiMonte, G. Bellomo, H. Thor, P. Nicotera and S. Orrenius, Menadione-induced cytotoxicity is associated with protein thiol oxidation and alteration in intracellular Ca2+ homeostasis, Arch. Biochem. Biophvs. 235:343 (1984).CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1989

Authors and Affiliations

  • Robin S. Goldstein
    • 1
  • Randall S. Sozio
    • 1
  • Joan B. Tarloff
    • 1
  • Jerry B. Hook
    • 1
  1. 1.Smith Kline & French LaboratoriesDepartment of Investigative ToxicologyKing of PrussiaUSA

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