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Related Experiment Videos

Cyclosporine A-induced decrease in calbindin-D 28 kDa in rat kidney but not in cerebral cortex and cerebellum

M C Varela1, A Arce, B Greiner

  • 1Preclinical Safety, Toxicology, Novartis Pharma AG, Basel, Switzerland.

Biochemical Pharmacology
|August 26, 1998
PubMed
Summary

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Cyclosporine A (CsA) reduces calbindin-D 28 kDa in rat kidneys but not in the brain. This study indicates CsA does not significantly impact brain calbindin-D 28 kDa levels at relevant doses.

Area of Science:

  • Nephrology
  • Neuroscience
  • Pharmacology

Background:

  • Calbindin-D 28 kDa (CABP-D) is a calcium-binding protein crucial for calcium transport in tissues like the kidney and brain.
  • Previous research indicated Cyclosporine A (CsA) significantly decreases CABP-D levels in rat kidneys.

Purpose of the Study:

  • To investigate the effect of CsA on CABP-D 28 kDa levels in the rat brain.
  • To compare CsA concentrations and CABP-D 28 kDa localization in kidney and brain tissues.

Main Methods:

  • Male Wistar rats were administered varying doses of CsA orally for 12 days.
  • Quantification of CABP-D 28 kDa protein and CsA in kidney, cerebral cortex, and cerebellum homogenates.
  • Immunohistochemistry was used to assess CABP-D 28 kDa localization in tissue sections.

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Main Results:

  • CsA significantly decreased kidney CABP-D 28 kDa in a dose-dependent manner, localized in tubular epithelial cells.
  • CsA did not alter CABP-D 28 kDa levels in the rat brain (cortex and cerebellum).
  • CsA concentrations were substantially higher in the kidney compared to the brain cortex; CsA was undetectable in the cerebellum.

Conclusions:

  • CsA treatment at clinically relevant doses does not appear to affect calbindin-D 28 kDa levels in the rat brain.
  • The differential distribution and concentration of CsA in kidney versus brain may explain the distinct effects on CABP-D 28 kDa.