EARLY ADMINISTRATION OF PDTC IN ADRIAMYCIN NEPHROPATHY: EFFECT ON PROTEINURIA, CORTICAL TUBULOINTERSTITIAL INJURY, AND NF- B ACTIVATION

Autor:	Gopala K. Rangan, Yuet-Ching Tay, David Harris, Yiping Wang
Rok vydání:	2001
Předmět:	Male medicine.medical_specialty Kidney Cortex Pyrrolidines Time Factors Critical Care and Intensive Care Medicine Antioxidants Monocytes Lipid peroxidation chemistry.chemical_compound Pyrrolidine dithiocarbamate Polyuria Thiocarbamates In vivo Internal medicine medicine Animals Doxorubicin Rats Wistar Proteinuria business.industry Monocyte NF-kappa B General Medicine medicine.disease Rats Kidney Tubules medicine.anatomical_structure Endocrinology chemistry Nephrology Kidney Diseases Lipid Peroxidation medicine.symptom business medicine.drug Kidney disease
Zdroj:	Renal Failure. 23:773-780
ISSN:	1525-6049 0886-022X
DOI:	10.1081/jdi-100108188
Popis:	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.
Databáze:	OpenAIRE
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