ZFIN ID: ZDB-PUB-050104-9
Acute renal failure in zebrafish: a novel system to study a complex disease
Hentschel, D.M., Park, K.M., Cilenti, L., Zervos, A.S., Drummond, I., and Bonventre, J.V.
Date: 2005
Source: American journal of physiology. Renal physiology   288(5): F923-F929 (Journal)
Registered Authors: Drummond, Iain, Hentschel, Dirk
Keywords: animal model; drug development; glomerular filtration; fluorescence
MeSH Terms:
  • Acute Kidney Injury/chemically induced*
  • Acute Kidney Injury/physiopathology
  • Animals
  • Anti-Bacterial Agents/toxicity*
  • Antineoplastic Agents/toxicity
  • Cisplatin/toxicity
  • Disease Models, Animal*
  • Gentamicins/toxicity*
  • Glomerular Filtration Rate
  • Kidney/growth & development
  • Kidney/pathology
  • Kidney/physiology
  • Lysosomes/metabolism
  • Lysosomes/pathology
  • Mice
  • Mice, Inbred BALB C
  • Mitochondrial Proteins
  • Phospholipids/metabolism
  • Serine Endopeptidases/metabolism
  • Zebrafish*
PubMed: 15625083 Full text @ Am. J. Physiol. Renal Physiol.
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ABSTRACT
Acute renal failure (ARF) is characterized by a very high mortality essentially unchanged over the past 40 years. Simple vertebrate models are needed to improve our understanding of ARF and facilitate the development of novel therapies for this clinical syndrome. Here we demonstrate that gentamicin, a commonly used nephrotoxic antibiotic, causes larval zebrafish to develop ARF characterized by histological and functional changes that mirror aminoglycoside toxicity in higher vertebrates and inability of zebrafish to maintain fluid homeostasis. We developed a novel method to quantitate renal function in larval zebrafish, and demonstrate a decline in glomerular filtration rate after gentamicin exposure. The anti-neoplastic drug cisplatin, whose use in humans is limited by kidney toxicity, also causes typical histological changes and a decline in renal function in larval zebrafish. A specific inhibitor of Omi/HtrA2, a serine protease implicated in cisplatin-induced apoptosis, prevented renal failure and increased survival. This protective effect was confirmed in a mouse model of cisplatin-induced nephrotoxicity. Therefore zebrafish provides a unique model system, amenable to genetic manipulation and drug screening, to explore the pathophysiology of ARF and establish novel therapies with potential use in mammals.
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