Chronic interstitial fibrosis in the rat kidney induced by long-term (6-mo) exposure to lithium

Am J Physiol Renal Physiol. 2013 Feb 1;304(3):F300-7. doi: 10.1152/ajprenal.00182.2012. Epub 2012 Nov 21.

Abstract

There is a lack of suitable animal models that replicate the slowly progressive chronic interstitial fibrosis that is characteristic of many human chronic nephropathies. We describe a chronic long-term (6-mo) model of lithium-induced renal fibrosis, with minimal active inflammation, which mimics chronic kidney interstitial fibrosis seen in the human kidney. Rats received lithium via their chow (60 mmol lithium/kg food) daily for 6 mo. No animals died during the exposure. Nephrogenic diabetes insipidus was established by 3 wk and persisted for the 6 mo. Following metabolic studies, the animals were killed at 1, 3, and 6 mo and the kidneys were processed for histological and immunohistochemical studies. Progressive interstitial fibrosis, characterized by increasing numbers of myofibroblasts, enhanced transforming growth factor-β(1) expression and interstitial collagen deposition, and a minimal inflammatory cellular response was evident. Elucidation of the underlying mechanisms of injury in this model will provide a greater understanding of chronic interstitial fibrosis and allow the development of intervention strategies to prevent injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chronic Disease
  • Collagen / metabolism
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Fibrosis
  • Kidney / drug effects*
  • Kidney / metabolism
  • Kidney / pathology*
  • Lithium / adverse effects*
  • Lithium / pharmacology*
  • Male
  • Nephritis, Interstitial / chemically induced*
  • Nephritis, Interstitial / metabolism
  • Nephritis, Interstitial / pathology
  • Rats
  • Rats, Wistar
  • Time Factors
  • Transforming Growth Factor beta1 / metabolism

Substances

  • Transforming Growth Factor beta1
  • Collagen
  • Lithium