Chronic cyclosporin A (CsA) nephrotoxicity in the rat: The effect of calcium blockade with verapamil

M. G. Shaikh, S. D. Heys, P. A.J. Brown, P. H. Whiting*

*Corresponding author for this work

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Renal structure and function were assessed in groups of male Sprague-Dawley rats, either surgically intact (SI) or nephrectomized (N), treated with either CsA alone (20 mg/kg, p.o.) or in combination with verapamil (VER; 10 mg/kg/day, i.p.) daily for up to 28 days. Compared to vehicle treated controls, reduced creatinine clearance rates (CCR, mean ± s.e.m.) were noted following CsA treatment in SI animals on days 21 and 28 (279 ± 4 vs 196 ± 20 and 296 ± 13 vs 122 ± 13 ml/h/kg, respectively, both P < 0.05). However, CCR was around 60% of pretreatment values in all N animals from day 7 onwards. A two to three-fold elevation in urinary N-acetyl-β-D-glucosaminidase activity was noted from day 7 to 28 in all CsA treated animals. In addition, a similar severity of both renal tubular basophilia and corticomedullary microcalcification (but not proximal tubular vacuolation), was noted at all time points in animals receiving CsA alone. Co-treatment with VER reduced the severity of microcalcification in CsA groups, particularly N animals, increased CCR on day 14 in the SI (196 ± 23 vs 391 ± 64) and days 21 and 28 in N (141 ± 14 vs 357 ± 32 and 152 ± 28 vs 261 ± 20) groups, respectively but had no effect on the magnitude of enzymuria, despite significantly increased trough whole blood CsA levels (20-30%) in both SI and N groups. These results indicate that calcium blockade reduces both structural and functional features of chronic CsA nephrotoxicity.

Original languageEnglish
Pages (from-to)389-396
Number of pages8
JournalInternational journal of experimental pathology
Volume74
Issue number4
Publication statusPublished - Aug 1993

Keywords

  • calcium blockade
  • cyclosporin A
  • nephrotoxicity
  • rat

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Cell Biology

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