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Histochemistry

, Volume 71, Issue 2, pp 235–248 | Cite as

Quantification of nephrotoxicity in rabbits by automated morphometry of alkaline phosphatase stained kidney sections

  • E. D. Wachsmuth
Article

Summary

Male and female rabbits were injected intravenously with a single dose of either cefroxadine or cefsulodin or cephaloridine. Quantitative determinations of the activity of two brush border membrane enzymes, aminopeptidase and alaline phosphatase, were made in homogenates of cortical kidney tissue, in the urine and morphometrically in proximal tubules of cryostat sections. Morphometry was done by classification and enumeration of proximal tubule sections with the same level of enzyme reaction product using a microscopic television analysis system. By comparison with the control values, no changes were detectable 24 h after the injection of up to 1.2 g cefroxadine or cefsulodin per kg body weight. By contrast, after 300 mg/kg cephaloridine, the concentrations of the two enzymes were decreased in a large number of proximal tubules, i.e. the bursh border membranes, and concomitantly cell degeneration and necrosis took place. Alkaline phosphatase activity in sections and tissue homogenates was reduced to a greater extent than aminopeptidase activity. A corresponding, significant increase in enzymic activity in the urine was only demonstrable in respect of aminopeptidase. The classification of proximal tubules in tissue sections by television analysis on the basis of alkaline phosphatase reaction product concentration appears to be a reliable measure for detecting and quantifying toxic effects on proximal tubules of kidney.

Keywords

Alkaline Phosphatase Proximal Tubule Brush Border Membrane Television Analysis Aminopeptidase Activity 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Ahrens T, Vischer W, Imhof P, Fuellhaas J, Zak O, and Kradolfer F (1979) Human pharmacology of CGP 7174/E (SCE-129) and initial results of clinical trials in Europe. Drugs Exp Clin Res 5:61–70Google Scholar
  2. Atkinson RM, Caisey JD, Currie JP, Middleton TR, Pratt DAH, Sharpe HM, and Tomich EG (1966) Subacute toxicity of cephaloridine to various species. Toxicol Appl Pharmacol 8:407–428Google Scholar
  3. Castaner J, and Playle AC (1977) CGP 9000, Antibiotic. Drugs of the future (E) 2:574–578Google Scholar
  4. Currie GA, Little PJ, and McDonald SJ (1966) The localisation of cephaloridine and nitrofurantoin in the kidney. Nephron 3:282–288Google Scholar
  5. Dubach UC, and Schmidt U (1979) Diagnostic significance of enzymes and proteins in urine. Hans Huber, Bern Stuttgart ViennaGoogle Scholar
  6. Mondorf AW, Zegelmann M, and Mackenrodt G (1976) Die klinisch-diagnostische Bedeutung lokalisationsspezifischer Enzyme im Harn. Infection 4, Suppl. 3:269–271Google Scholar
  7. Raab W, und Moerth C (1976) Renal effects of gentamicin and cephaloridine. Arzneim Forsch 26:377–379Google Scholar
  8. Sack K (1976) Die Differenzierung der Nierenverträglichkeit verschiedener Cephalosporine im Tierexperiment. Infection 4, Suppl. 3:237–245Google Scholar
  9. Serra J, Müller W (1974) In quantitative image analysis. The problem of resolution and errors caused by measuring logic, Leitz Sci Tech Information Suppl I, 4:117–124Google Scholar
  10. Serra J (1974) Theoretical bases of the leitz texture analyser system. Leitz Sci Tech Information Suppl I, 4:125–136Google Scholar
  11. Suginaka H, Shimatani M, Kotani S, Ogawa M, Hama M, and Kosaki G (1979) Antibacterial mechanism of cefsulodine against pseudomonas aeruginosa and escherichia coli. Microbiol Lett 5:177–179Google Scholar
  12. Taguchi T, Nakano Y, Jikuya K, Mashimo K, Kunii O, Fukaya K, and Yamaguchi N (1979) Phase I clinical studies on cefsulodin (SCE-129) administered intramuscularly. Chemotherapy (J) 27:136–145Google Scholar
  13. Terhorst B, Lymberopoulos S, and Buss H (1971) Tierexperimentelle und klinische Untersuchungen zur Frage der Nephrotoxizität von Cephaloridin. Med Welt 22:1565–1569Google Scholar
  14. Tune BM (1975) Relationship between the transport and toxicity of cephalosporines in the kidney. J Infect Dis 132:189–194Google Scholar
  15. Wachsmuth ED, Fritze I, and Pfleiderer G (1966) An aminopeptidase occurring in pig kidney. An improved method of preparaton: Physical and enzymic properties. Biochemistry 5:169–174Google Scholar
  16. Waschsmuth ED, and Hiwada K (1974) Alkaline phosphatase from pig kidney. Method of purification and molecular properties. Biochem J 141:273–282Google Scholar
  17. Wachsmuth ED (1976) Aspects of regulation in kidney at the enzymic level: Aldolase isozymes, aminopeptidase and alkaline phosphatase. In: Schmidt U, and Dubach UC (eds), Renal metabolism in relation to renal function. Hans Huber, Bern, pp 381–391Google Scholar
  18. Wachsmuth ED and Stoye JP (1976) The differnetiation of proximal and distal tubules in the male rat kidney: The appearance of aldolase isozymes, aminopeptidase and alkaline phosphatase during ontogeny. Histochemistry 47:315–337Google Scholar
  19. Wachsmuth ED and Wirz H (1979) Relevance of enzyme evaluations in 24h urine to rat kidney injury caused by i.v. cephaloridine injection. In: Dubach UC, Schmidt U (eds) Diagnostic significance of enzymes and proteins in urine. Hans Huber, Bern Stuttgart Vienna, pp 88–104Google Scholar
  20. Wellwood JM, Lovell D, Thompson AE, and Tighe JR (1976) Renal damage caused by gentamicin: A study of the effects on renal morphology and urinary enzyme excretion. J Pathol 118:171–182Google Scholar
  21. Wirz H, Vischer WA, Füllhaas J, and Imhof PR (1978) Pharmacokinetics of CGP 9000, a new orally active cephalosporin, in healthy volunteers. 10th. Int. Congr Chemotherapy, Zürich, Abstr. 323. In: Siegenthaler W, Lüthy R (eds) Current chemotherapy, vols 1 and 2. American Society for Microbiology, WashingtonGoogle Scholar
  22. Zekert F, and Mautner-Markhof C (1976) Untersuchungen über die normale Ausscheidung im Harn des Menschen und der Ratte. Wien Klin Wochenschr 88:467–469Google Scholar

Copyright information

© Springer-Verlag 1981

Authors and Affiliations

  • E. D. Wachsmuth
    • 1
  1. 1.Research Department, Pharmaceuticals DivisionCIBA-GEIGY LimitedBasleSwitzerland

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