Temporary warm ischaemia, 5/6 nephrectomy and single uranyl nitrate administration--comparison of three models intended to cause renal fibrosis in rats.
In patients the progression of pathologic renal processes after the treatment of primary disease is a problem of increasing importance and therapeutic strategies are insufficient till now. The aim of this paper was to search for rat models of interstitial fibrosis as a basis for testing therapeutic strategies to prevent end-stage renal failure. Experiments were done on adult female Wistar rats (Han:Wist) to investigate long-term consequences of temporary warm ischaemia, 5/6 nephrectomy (5/6 NX) and single uranyl nitrate (UN) administration (0.3 or 0.5 mg/ 100 g body wt. intraperitoneally). Observation time was 20 weeks after injury in each group. Creatinine clearance, urinary protein excretion and hydroxy-proline (OH-proline) concentration in renal tissue were measured and light microscopic investigations were done to characterise both quality and time course of long-term renal damage in relation to matched control animals. Temporary warm ischaemia and 5/6 NX did not cause any fibrotic changes during the 20 weeks observation period. The higher UN dose led to decreased creatinine clearance, increased urinary protein excretion and enhanced OH-proline concentration in renal tissue. Morphologic investigations showed fibrotic areas containing strongly dilated and atrophic tubules with thickened basal membranes. These effects can be seen from week four after UN administration up to the end of the observation period. In conclusion, administration of one single dose of UN is a simple procedure to induce interstitial renal fibrosis as an experimental model to investigate therapeutic strategies for their prevention.
Appenroth
D
D
Institute of Pharmacology and Toxicology, Friedrich Schiller University Jena, Germany. dapp@mti-n.uni-jena.de
Lupp
A
A
Kriegsmann
J
J
Sawall
S
S
Splinther
J
J
Sommer
M
M
Stein
G
G
Fleck
C
C
D000818:Animals; D003404:Creatinine / Q000097:blood / Q000652:urine; D004195:Disease Models, Animal; D005260:Female; D005355:Fibrosis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D006909:Hydroxyproline / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D009392:Nephrectomy; D009395:Nephritis, Interstitial / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D011507:Proteinuria; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000473:pathology*; D013997:Time Factors; D014502:Uranyl Nitrate / Q000633:toxicity*
D014502:Uranyl Nitrate; D003404:Creatinine; D006909:Hydroxyproline