Related Experiment Videos
Acute renal failure in zebrafish: a novel system to study a complex disease
Dirk M Hentschel1, Kwon Moo Park, Lucia Cilenti
1Department of Medicine, Renal Division, Brigham and Women's Hospital, Boston, MA 02115, USA.
American Journal of Physiology. Renal Physiology
|December 31, 2004
Summary
Larval zebrafish exposed to gentamicin or cisplatin develop acute renal failure (ARF). Zebrafish models offer a new way to study ARF and test therapies for kidney disease.
Area of Science:
- Nephrology
- Toxicology
- Developmental Biology
Background:
- Acute renal failure (ARF) has a high mortality rate and lacks effective treatments.
- Simple vertebrate models are needed to understand ARF and develop new therapies.
Purpose of the Study:
- To establish larval zebrafish as a model for ARF.
- To investigate gentamicin and cisplatin-induced nephrotoxicity in zebrafish.
- To identify potential therapeutic targets for ARF.
Main Methods:
- Larval zebrafish were exposed to gentamicin and cisplatin.
- Renal function was assessed using a novel quantitative method measuring glomerular filtration rate.
- Histological changes and survival rates were analyzed.
- An Omi/HtrA2 inhibitor was tested for protective effects.
Main Results:
- Gentamicin induced ARF in zebrafish, mirroring aminoglycoside toxicity in mammals.
- Cisplatin caused similar renal damage and functional decline.
- A specific Omi/HtrA2 inhibitor protected zebrafish from cisplatin-induced nephrotoxicity.
- This protective effect was validated in a mouse model.
Conclusions:
- Larval zebrafish serve as a valuable model for studying ARF pathophysiology.
- Zebrafish models facilitate drug screening for novel ARF therapies.
- Targeting Omi/HtrA2 shows potential for treating cisplatin-induced kidney injury.