Retinoic acid exacerbates experimental radiation nephropathy. Radiat Res 2002 Feb;157(2):199-203
Date
02/12/2002Pubmed ID
11835684DOI
10.1667/0033-7587(2002)157[0199:raeern]2.0.co;2Scopus ID
2-s2.0-0036152353 (requires institutional sign-in at Scopus site) 20 CitationsAbstract
Studies have shown that angiotensin-converting enzyme inhibitors and an angiotensin II receptor blocker can delay, but cannot reverse, the progression of experimentally induced radiation nephropathy. In an effort to find a method for reversing injury, three agents were tested in a rat model of radiation nephropathy. Pirfenidone (a phenyl-pyridone antifibrotic) and thiaproline (an inhibitor of collagen deposition) were not capable of retarding the development of radiation nephropathy. However, all-trans retinoic acid (an anti-inflammatory agent) exacerbated radiation nephropathy. We speculated that the detrimental effects of retinoic acid might be the result of stimulation of renal cell proliferation. However, retinoic acid had no effect on tubular or glomerular cell proliferation in normal animals and did not enhance radiation-induced proliferation. A recent report that retinoic acids inhibit nitric oxide production suggested an alternative mechanism, since inhibition of production of nitric oxide is known to exacerbate radiation nephropathy. Experiments demonstrated that retinoic acid exacerbated the radiation-induced drop in renal production of nitric oxide, suggesting that the detrimental effect of all-trans retinoic acid might be explained by inhibition of renal nitric oxide activity. Particularly in view of the recent clinical report of enhancement of radiation nephropathy by retinoic acid in patients receiving bone marrow transplantation, the combination of retinoic acid and renal irradiation should be carried out with great caution.
Author List
Moulder JE, Fish BL, Regner KR, Cohen EP, Raife TJAuthor
Kevin R. Regner MD Interim Chair, Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsAnti-Inflammatory Agents, Non-Steroidal
Cell Division
Extracellular Matrix
Fibrosis
Hypertension, Renal
Kidney
Kidney Diseases
Kidney Failure, Chronic
Proteinuria
Pyridones
Radiation Injuries, Experimental
Rats
Rats, Inbred Strains
Thiazoles
Thiazolidines
Tretinoin
Uremia
Whole-Body Irradiation
