Effects of lactational cyclosporine A use on rat pups

Pediatr Transplant. 2006 Jun;10(4):454-60. doi: 10.1111/j.1399-3046.2006.00495.x.

Abstract

We aimed to evaluate the structural and functional changes in the thymus and kidneys of rat pups whose mothers were given cyclosporine A (CsA) during lactational period. Six adult nursing Wistar rats and their 30 pups were studied. Rat pups were divided into four groups as follows: 21-day treated group and 21-day placebo group, each including 10 breastfeeding pups sacrificed on the 21st day, whose mothers were given CsA or placebo, respectively (infancy groups) and, 60-day treated group and 60-day placebo group, each including five breastfeeding pups sacrificed on the 60th day, whose mothers were given CsA or placebo, respectively (puberty groups). While CsA levels of mother rats were very high, CsA levels of 21-day treated group pups were zero. There were no renal histomorphometric differences between study and control pups in both age groups. Renal function parameters showed significant differences between study and control pups in the infancy group: the 21-day treated group pups had significantly lower urine volume, proteinuria, FE(Na) and urinary NAG/creatinine ratio. GFR was also lower in the 21-day treated group, but the difference was not significant, and serum creatinine levels were also not different. Renal function differences were not present among the pubertal pups. Thymic corticomedullary ratio of the 21-day treated group was significantly higher than the 21-day placebo group, while there was no difference between the 60-day treated group and 60-day placebo group. There were no significant changes in the number and distribution of CD3+, CD4+, and CD8+ thymocytes between study and control pups in both age groups. In conclusion, breastfeeding by CsA-treated mother rats induced structural alterations in the thymus and functional changes in the kidneys of the rat pups during infancy. Disturbances in the kidneys and thymus mostly improved after CsA exposure was over.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylglucosaminidase / blood
  • Animals
  • Animals, Newborn
  • Body Weight / drug effects
  • Creatinine / blood
  • Cyclosporine / pharmacology*
  • Female
  • Glomerular Filtration Rate / drug effects
  • Immunosuppressive Agents / pharmacology*
  • Kidney / drug effects
  • Kidney / pathology
  • Kidney / physiopathology
  • Kidney Glomerulus / drug effects
  • Kidney Glomerulus / physiopathology
  • Kidney Tubules / drug effects
  • Kidney Tubules / physiopathology
  • Lactation / drug effects*
  • Maternal-Fetal Exchange / drug effects
  • Phosphorus / blood
  • Pregnancy
  • Prenatal Exposure Delayed Effects / chemically induced
  • Prenatal Exposure Delayed Effects / physiopathology
  • Proteinuria
  • Random Allocation
  • Rats
  • Rats, Wistar
  • Thymus Gland / drug effects
  • Thymus Gland / pathology

Substances

  • Immunosuppressive Agents
  • Phosphorus
  • Cyclosporine
  • Creatinine
  • Acetylglucosaminidase