Isotretinoin ameliorates renal damage in experimental acute renal allograft rejection.

作者: Eva Kiss , Judith Adams , Hermann-Josef Gr??ne , J??rgen Wagner

DOI: 10.1097/01.TP.0000066354.31050.5A

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摘要: BACKGROUND Retinoic acids, derivatives of vitamin A, act through retinoid receptors that are expressed in renal and immunocompetent cells (B T cells; monocytes macrophages). In experimental models glomerulonephritis interstitial disease, retinoids were shown to reduce both glomerular tubular damage inflammation. We therefore examined whether cellular rejection a model acute allograft rejection. METHODS Kidneys Fisher rats (F344, RT11v1) orthotopically grafted Lewis (RT11). Animals killed 7 or 14 days after transplantation. Rats undergoing transplantation treated with isotretinoin (13 cis-retinoic acid) at low dose 2 mg/kg body weight per day (LD isotretinoin) high 20 (HD vehicle. RESULTS At 14, albuminuria was reduced by approximately 70% (vehicle: 1.1+/-0.2 mg/24 hr vs. LD isotretinoin: 0.32+/-0.1 hr; P<0.001). serum creatinine levels significantly higher the vehicle-treated group than HD isotretinoin-treated (P<0.05). Both vascular injury compared (score 14: 20.1+/-5.1 vehicle 57.8+/-9.9, P<0.01), (score: 6.8+/-1.0 10.6+/-0.9 P<0.05), number macrophages cytotoxic cells. Isotretinoin also lessened tubulointerstitial damage, cell proliferation, infiltrating tubulointerstitium. CONCLUSIONS ameliorated functional, vascular, glomerular, lesions graft Although current study did not definitely eliminate possibility only delayed process, retinoic acid may provide new approach treatment injury.

参考文章(23)
Jürgen Floege, Ingo Lehrke, Volker Haxsen, Christian Morath, Rüdiger Waldherr, Eberhard Ritz, Claudius Dechow, Jürgen Wagner, Effects of Retinoids on the TGF-β System and Extracellular Matrix in Experimental Glomerulonephritis Journal of The American Society of Nephrology. ,vol. 12, pp. 2300- 2309 ,(2001) , 10.1681/ASN.V12112300
C.B. Bunker, M.H.A. Rustin, Pauline M. Dowd, Isotretinoin treatment of severe acne in posttransplant patients taking cyclosporine Journal of The American Academy of Dermatology. ,vol. 22, pp. 693- 694 ,(1990) , 10.1016/S0190-9622(08)81050-X
Reinhard Andreesen, Marina Kreutz, Jana Fritsche, Ute Ackermann, Stefan W. Krause, Retinoic Acid Inhibits Monocyte to Macrophage Survival and Differentiation Blood. ,vol. 91, pp. 4796- 4802 ,(1998) , 10.1182/BLOOD.V91.12.4796
Bedford Pa, Knight Sc, The effect of retinoids on dendritic cell function. Clinical and Experimental Immunology. ,vol. 75, pp. 481- ,(1989)
Pierre Chambon, A decade of molecular biology of retinoic acid receptors. The FASEB Journal. ,vol. 10, pp. 940- 954 ,(1996) , 10.1096/FASEBJ.10.9.8801176
Ulrich Kintscher, Stephan Goetze, Shu Wakino, Sarah Kim, Sunil Nagpal, Roshantha A.S Chandraratna, Kristof Graf, Eckart Fleck, Willa A Hsueh, Ronald E Law, Peroxisome proliferator-activated receptor and retinoid X receptor ligands inhibit monocyte chemotactic protein-1-directed migration of monocytes. European Journal of Pharmacology. ,vol. 401, pp. 259- 270 ,(2000) , 10.1016/S0014-2999(00)00461-1
P. D. Pigatto, L. Bersani, F. Colotta, M. Morelli, G. F. Altomare, M. M. Polenghi, Effect of retinoids on natural killer cell activity. Archives of Dermatological Research. ,vol. 278, pp. 507- 509 ,(1986) , 10.1007/BF00455175
Miroslav Malkovský, Andrew J. Edwards, Ruth Hunt, Lesley Palmer, Peter B. Medawar, T-cell-mediated enhancement of host-versus-graft reactivity in mice fed a diet enriched in vitamin A acetate. Nature. ,vol. 302, pp. 338- 340 ,(1983) , 10.1038/302338A0
M. Harms, Isotretinoin: 10 years on. Dermatology. ,vol. 186, pp. 81- 82 ,(1993) , 10.1159/000247311