ABSTRACT:Iron overload disorders are characterized by the accumulation of iron in cells of the liver, spleen, heart and other organs. Previous investigations indicate that due to the central role of iron in oxy-radical chemistry and in lipid peroxidation, cell injury by oxygen-free radicals may be a possible cause of iron toxicity. While the protective effect of vitamin E against oxy-radical damage is well documented, cobalt has been reported only recently to have antioxidant effects in vitro by competing with iron as a catalyst in the Haber-Weiss reaction. We examined cobalt for protective effects in vivo and compared its antioxidant actions with vitamin E. Three groups of adult male Wistar rats (n=32) were injected subcutaneously(sc) with iron-dextran (125mg/kg BW) followed immediately and for 3 weeks thereafter (3x/wk) by the injection intraperitoneally of cobalt chloride(15mg/kg BW; group #3, n=12), intramuscularly with vitamin E (100 mg/kg BW; group #4, n=12) or no further treatment (group #2, n=8). Another control group(#1) of 6 rats was injected sc with normal saline in the absence of iron dextran. One day after the last injection blood was collected then liver, spleen and intestines were removed and processed for biochemical and histopathological analyses. These clearly showed that both cobalt (#3) and vitamin E (#4) significantly decreased (p<0.001) the levels of hypoxanthine and lipid peroxidation in all tissues. Cobalt and vitamin E also reduced(p<0.001) tissue myeloperoxidase (MPO) activity in all tissues but intestines where cobalt was ineffective. Tissue glutathione levels remained unaffected by either treatment. Cobalt therapy, however, increased hematocrit, hemoglobin and the MCV (0.05). The most striking finding was the presence of liver granulomas in most of the animals in #2 (71%) and #3 (66.6%). In contrast to cobalt, vitamin E effectively reduced the appearance of granulomas to 33.3% of the animals in group #4 while granulomas were completely absent in all animals in #1. Together these findings suggest that cobalt provides a significant antioxidant effect in vivo and, thus, extend earlier in vitro observations. Cobalt, while similarly affective in preventing cytotoxicity in iron overload it is less efficient in inhibiting granuloma formation in the liver.