title: Chronic interstitial fibrosis in the rat kidney induced by long-term (6-mo) exposure to lithium.
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.
authors.affiliation: Department of Medicine, Dunedin School of Medicine, University of Otago, P.O. Box 913, Dunedin, 9016, New Zealand. rob.walker@otago.ac.nz
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Walker
authors.forename: John P
authors.initials: JP
authors.lastname: Leader
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Bedford
authors.forename: Glenda
authors.initials: G
authors.lastname: Gobe
authors.forename: Gerard
authors.initials: G
authors.lastname: Davis
authors.forename: Frederiek E
authors.initials: FE
authors.lastname: Vos
authors.forename: Sylvia
authors.initials: S
authors.lastname: deJong
authors.forename: John B W
authors.initials: JB
authors.lastname: Schollum
mesh_terms: D000818:Animals; D002908:Chronic Disease; D003094:Collagen / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005355:Fibrosis; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D008094:Lithium / Q000009:adverse effects* / Q000494:pharmacology*; D008297:Male; D009395:Nephritis, Interstitial / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D053773:Transforming Growth Factor beta1; D003094:Collagen; D008094:Lithium