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

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

Author information

1
Department of Medicine, Dunedin School of Medicine, University of Otago, P.O. Box 913, Dunedin, 9016, New Zealand. rob.walker@otago.ac.nz

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.

PMID:
23171555
DOI:
10.1152/ajprenal.00182.2012
[Indexed for MEDLINE]
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