EARLY ADMINISTRATION OF PDTC IN ADRIAMYCIN NEPHROPATHY: EFFECT ON PROTEINURIA, CORTICAL TUBULOINTERSTITIAL INJURY, AND NF- B ACTIVATION
- 1 January 2001
- journal article
- Published by Taylor & Francis Ltd in Renal Failure
- Vol. 23 (6), 773-780
- https://doi.org/10.1081/jdi-100108188
Abstract
The persistence of NF-kappaB independent inflammatory signals in the cortical tubulointerstitium may explain the incomplete suppression of interstitial monocyte accumulation by the antioxidant NF-kappaB inhibitor, pyrrolidine dithiocarbamate (PDTC), in nephrotic rats with established Adriamycin nephropathy (AN). Because PDTC is known to have anti-proteinuric effects, in this study we investigated whether earlier commencement, during the pre-nephrotic phase of AN, would be more effective in reducing interstitial monocyte accumulation. Male Wistar rats with AN received either vehicle or PDTC (50 mg/kg bd i.p.i.) from d7 until d30 (n = 8 per group). On d30, PDTC reduced renal cortical lipid peroxidation (43%), wet kidney weight and tubulointerstitial injury in AN, but did not decrease proteinuria. Accordingly, inhibition of interstitial ED-1 accumulation remained incomplete (52%). Interestingly, the early administration of PDTC in AN, induced polyuria and renal cortical NF-kappaB DNA-binding activity was reduced by only 35%. These results suggest that: (i) the combination of an anti-proteinuric agent with PDTC may be required to completely suppress interstitial monocyte cell accumulation in AN and, (ii) the timing and duration of PDTC therapy are an important determinant of its efficacy to reduce NF-kappaB activation, in vivo.Keywords
This publication has 8 references indexed in Scilit:
- Transcription factor-κB (NF-κB) and renal diseaseKidney International, 2001
- Protein traffic activates NF-kB gene signaling and promotes MCP-1–dependent interstitial inflammationAmerican Journal of Kidney Diseases, 2000
- The Role of Protein Traffic in the Progression of Renal DiseasesAnnual Review of Medicine, 2000
- Inhibition of nuclear factor-κB activation reduces cortical tubulointerstitial injury in proteinuric ratsKidney International, 1999
- Activation of transcription factor NF-κB in experimental glomerulonephritis in ratsBiochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 1996
- Evidence for the Involvement of Vasopressin in the Pathophysiology of Adriamycin-induced Nephropathy in RatsNephron, 1996
- Dithiocarbamates as potent inhibitors of nuclear factor kappa B activation in intact cells.The Journal of Experimental Medicine, 1992
- Effect of timing of cyclosporine administration on recovery from renal ischemia in ratsJournal of Surgical Research, 1991