Additive effect of PPAR-م agonist and ARB in treatment of experimental IgA nephropathy
- نوع فایل : کتاب
- زبان : انگلیسی
- مؤلف : Kar Neng Lai & Loretta Y. Y. Chan & Hong Guo & Sydney C. W. Tang & Joseph C. K. Leung
- چاپ و سال / کشور: 2011
Description
Our recent in vitro study demonstrated peroxisome proliferator-activated receptor-م (PPAR.م) agonist potentiated the anti-inflammatory effect of angiotensin receptor blocker (ARB) in tubular epithelial cell under milieu mimicking IgA nephropathy (IgAN). Here we studied the therapeutic effect of combining a PPAR-م agonist, rosiglitazone (Ros), with an ARB, losartan (Los), in experimental IgAN induced in Lewis rats by oral and intravenous immunization with bovine gamma-globulin (BGG). The rats were randomly divided into six groups: control, IgAN, IgAN with unilateral nephrectomy (IgAN/ 1K), and IgAN/1K receiving Ros, Los, or Ros + Los. Medication was given 1 week after nephrectomy until killing. Rats developing IgAN had hematuria, mesangial hypercellularity with IgA deposition, glomerular damage, and tubulointerstitial infiltration of CD25+ leukocytes accompanied by increased renal expression of TGF-â, AngII receptor subtype-1 (ATR1) and ICAM-1. The renal histopathology, albuminuria, and renal expression of TGF-â, ATR1 and ICAM-1 worsened with unilateral nephrectomy. Ros or Los reduced the renal expression of PCNA, TGF-â, ATR1, and ICAM-1 in IgAN rats with nephrectomy. Despite no difference between rats treated with monotherapy, combined therapy offered additive effect with decreased renal expression of TGF-â, ATR1 and ICAM-1 and attenuation of renal injury. Our animal study suggests combined PPAR-م agonist and ARB holds promise for future therapy for IgAN.
Pediatr Nephrol (2011) 26:257–266 DOI 10.1007/s00467-010-1703-y Received: 6 September 2010 / Revised: 21 October 2010 / Accepted: 22 October 2010 / Published online: 2 December 2010
