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Juvenile toxicity of cyclosporin in the rat

Linda Allais1, Fabienne Condevaux, Pierluigi Fant

  • 1MDS Pharma Services, 329 Impasse du Domaine Rozier, Les Oncins, 69210 Saint-Germain sur l'Arbresle, France. linda.allais@mdsinc.com

Reproductive Toxicology (Elmsford, N.Y.)
|April 29, 2009
PubMed

Insights

Cyclosporin exposure in young rats impaired immune responses and caused toxicity at higher doses. Adverse immune effects were only observed when systemic toxicity was also present.

Area of Science:

  • Immunotoxicology
  • Developmental Toxicology
  • Pharmacology

Background:

  • Cyclosporin is an immunosuppressive drug with potential developmental toxicity.
  • Understanding the dose-dependent effects of cyclosporin on developing immune systems is crucial.

Purpose of the Study:

  • To evaluate the impact of early-life cyclosporin exposure on immune system development and systemic toxicity in Sprague-Dawley rats.

Main Methods:

  • Rat pups (32 litters) received oral cyclosporin (0, 1, 3, or 10 mg/kg/day) from postnatal days 4-28.
  • Primary antibody response was assessed at 10 weeks of age.
  • Systemic toxicity, weight gain, and histopathology (heart, kidney) were evaluated.

Main Results:

  • A dose of 10 mg/kg/day caused persistent impairment of the primary antibody response.
  • Systemic toxicity, including pup mortality and reduced weight gain, occurred at 10 mg/kg/day.
  • Cardiovascular arteriopathy and kidney lesions (tubular basophilia, edema) were observed at 3 and 10 mg/kg/day.

Conclusions:

  • Pharmacological effects of cyclosporin were observed across all tested doses.
  • Adverse effects on immune system development were evident only at the highest dose, which also induced systemic toxicity.

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