DO INDOMETHACIN AND CIMETIDINE OR CU(CIMETADINE)(2) AFFECT THE NATURE OF SUPEROXIDE-DISMUTASE ACTIVITY IN THE LIVER OF COPPER-DEFICIENT RATS

1. Control and copper-deficient rats were treated with: (i) indomethacin; (ii) indomethacin in the presence of cimetidine; and (iii) indomethacin in the presence of Cu(cimetidine),. The levels of copper, zinc and manganese as well as the nature of superoxide dismutase activity in the liver were studied. 2. Copper deficiency caused a decrease of enzyme SOD activity, EDTA-insensitive (by 84%) and the appearance of nonenzyme SOD-like activity, EDTA-sensitive. The levels of copper and zinc decreased by 67% and 40% and the manganese level increased by 53%. 3. The above-mentioned treatments (i, ii, iii) of copper-deficient rats induced a progressive increase of enzyme SOD activity (by 19, 90 and 176%, respectively) without, however, changing nonenzyme SOD-like activity. It was only indomethacin treatment in the presence of Cu(cimetidine), that increased the copper level in control (by 82%) and copper-deficient (by 182%) rats. 4. The liver contained 4 CuZnSOD- and 1 MnSOD-isoenzymes, whose number and position on the gel were affected neither by copper deficiency nor by indomethacin treatment in the presence of Cu(cimetidine),. Copper deficiency significantly increased the MnSOD-band and reduced the CuZnSOD-bands, particularly that with pI similar to 5.7. Indomethacin in the presence of Cu(cimetidine), changed neither the MnSOD-band nor the reduced CuZnSOD-band with pI similar to 5.7, but restored to normal all the other CuZnSOD-bands.