Isotretinoin alleviates renal damage in rat chronic glomerulonephritis.
BACKGROUND
Retinoids, derivatives of vitamin A, have strong anti-inflammatory and antiproliferative properties. We previously demonstrated that the pan-agonists all-transretinoic acid (RA) and isotretinoin (13-cis RA) alleviate renal damage in rat acute glomerulonephritis (GN) induced by anti-Thy-1.1 mAb OX-7.


METHODS
The present study examined the effects of low dose and high dose treatment with isotretinoin in the chronic glomerulonephritis model, Thy-GN. Thy-GN was induced by a single intravenous injection of monoclonal antibody (mAb) 1-22-3 in uninephrectomized Wistar rats (N = 7 to 10 per group). Control and nephritic groups were treated with vehicle (veh), low dose isotretinoin (2 mg/kg body wt), or high dose isotretinoin (10 mg/kg body wt). The experiment was terminated 60 days after induction of Thy-GN.


RESULTS
In animals with Thy-GN, isotretinoin abrogated the increase in blood pressure and significantly reduced albuminuria. Glomerulosclerosis index, glomerular and interstitial cell counts, as well as the area of the interstitial space were significantly lower in nephritic rats treated with low and high dose isotretinoin compared to vehicle-treated nephritic controls. Treatment with isotretinoin also significantly reduced the number of glomerular and interstitial macrophages. The increase of transforming growth factor (TGF)-beta1, TGF receptor II and prepro-endothelin-1 gene expression in vehicle-treated nephritic rats was significantly attenuated by isotretinoin.


CONCLUSIONS
Treatment with isotretinoin significantly reduces glomerular and interstitial damage in rats with chronic glomerulonephritis as indicated by different functional and histological markers. Retinoids may provide a novel therapeutic option for the treatment of glomerulonephritis.
Schaier
M
M
Department of Nephrology, University of Heidelberg, Heidelberg, Germany.
Lehrke
I
I
Schade
K
K
Morath
C
C
Shimizu
F
F
Kawachi
H
H
Grone
H J
HJ
Ritz
E
E
Wagner
J
J
D000419:Albuminuria / Q000652:urine; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002908:Chronic Disease; D024042:Collagen Type I / Q000378:metabolism; D003404:Creatinine / Q000493:pharmacokinetics; D005353:Fibronectins / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D005921:Glomerulonephritis / Q000235:genetics / Q000473:pathology*; D015474:Isotretinoin / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects* / Q000473:pathology*; D007678:Kidney Glomerulus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007684:Kidney Tubules / Q000187:drug effects / Q000473:pathology; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D024042:Collagen Type I; D005353:Fibronectins; D003404:Creatinine; D015474:Isotretinoin