Superoxide dismutase (SOD) and catalase increase inducible nitric oxide (iNO) production by rat alveolar macrophages (AM).
Huffman LJ; Blake T; Felton C; Judy DJ; Castranova V
Toxicologist 1996 Mar; 30(1)(Pt 2):271
iNO has been implicated in cytotoxic reactions which occur in the presence of reactive oxygen species. However, NO also functions as an antioxidant in vivo. In the present study, we investigated the effect of SOD and catalase, antioxidant enzymes, on the regulation of iNO production by rat AM. AM were obtained by bronchoalveolar lavage from normal male rats and cultured for 1 hr before exposure to test agents. Media nitrate and nitrite (NOx) were used to index NO production and Northern blot analysis was used to detect iNO synthase (iNOS) mRNA. Incubation of AM with SOD (8,000 U/ml) or catalase (20,000 U/ml) for 18 h resulted in increases in NOx, as well as detectable iNOS mRNA levels. Exposure of AM to SOD or catalase for only 1 or 3 hr was sufficient to increase in NOx 18 hr later. Addition of pyrollidine dithiocarbamate (PDTC; 5uM) or cyc1ohexamide (CX; 10 uM) at the same time as SOD and catalase abolished increases in NOx. However, PDTC or CX were ineffective when added 6 hr after antioxidant exposure. These results suggest that SOD and catalase can directly stimulate the production of iNOS via a transcriptional mechanism. Antioxidant enzymes may be protective by selectively decreasing oxidant tone and increasing NO production.
Laboratory-animals; Animals; Animal-studies; Cytotoxins; Cytotoxicity; Cytotoxic-effects; Antioxidants; Antioxidation; In-vivo-studies; In-vivo-study; Exposure-levels; Exposure-assessment
The Toxicologist. Society of Toxicology 35th Annual Meeting, March 10-14,1996, Anaheim, California