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Background/Aim: Inhibition of nuclear factor κB with the antioxidant pyrrolidine dithiocarbamate (PDTC) reduced tubulointerstitial injury in Adriamycin nephropathy (AN), whereas N-acetylcysteine (NAC) was ineffective. Here we hypothesize that PDTC reduces the renal cortical expression of nuclear factor κB dependent cytokines in AN. Methods: Male Wistar rats received a single intravenous injection of doxorubicin hydrochloride (7.5 mg/kg). NAC (150 mg/kg twice daily i.p.), PDTC (50 mg/kg twice daily i.p.), or vehicle were commenced on day 14 and continued until day 30. Results: On day 30, mRNAs of selected cytokines were increased in AN (TNF-α 3.4-fold, MCP-1 5.1-fold, IL-10 2.7-fold, TGF-β1 3.5-fold, all p < 0.05) as determined by RT-PCR. PDTC reduced IL-10 and TGF-β1 mRNAs (p < 0.05), whereas the upregulation of MCP-1 and TNF-α mRNAs was not affected. In contrast, NAC increased TNF-α and IL-10 mRNAs (p < 0.05). Nuclear protein levels of activator protein-1 were increased in AN (4.4-fold, p < 0.01) and not significantly altered by PDTC (3.0-fold, p = 0.13) or NAC (5.2-fold, p = 0.18). Conclusions: The protective effects of PDTC in AN are not associated with a local reduction in TNF-α and MCP-1 gene expression. The latter may be due to continued transactivation by activator protein-1. These data also suggest that IL-10 and TGF-β1 mRNA expressions are PDTC dependent and have a role in mediating tubulointerstitial injury.Copyright © 2000 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]