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To provide a rationale for heme arginate's safety, the present study\nexamined the effects of various ferriporphyrins to sensitize human endothelial\ncells to free radical injury and to induce heme oxygenase and ferritin\nexpression. Heme arginate, unlike hematin, did not amplify oxidant-induced\ncytotoxicity mediated by hydrogen peroxide (5.3 +/- 2.4 versus 62.3 +/- 5.3%\n(51)Cr release, P <.0001) or by activated neutrophils (14.4 +/- 2.9 versus 41.1\n+/- 6.0%, P <.0001). Nevertheless, heme arginate efficiently entered endothelial \ncells similarly to hematin, since both markedly induced heme oxygenase mRNA (more\nthan 20-fold increase) and enzyme activity. Even with efficient permeation,\nendothelial cell ferritin content was only minimally increased by heme arginate\ncompared with a 10-fold induction by hematin; presumably less free iron was\nderived from heme arginate despite up-regulation of heme oxygenase. 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