The cytotoxic activities of human hemoglobin and diaspirin crosslinked hemoglobin

It is well known that hemoglobin (Hb) possesses many oxidative enzyme activities, including a pseudo-peroxidase activity. It has also been shown by many investigators that various peroxidases in the presence of hydrogen peroxide and a halide ion exert a potent cytotoxic activity toward various mammalian cell types. It has further been observed by various investigators that the administration of relatively large amounts of purified Hb or a Hb derivative to a host animal during resuscitation experiments leads to a number of unrelated types of tissue damage and cell damage in the host. The first objective of this investigation was to determine if the observed tissue and cell damage may be due to a cytotoxic activity that Hb may exert in vivo analogous to that of the peroxidases. We also showed some time ago that peroxidases are able to activate peritoneal macrophages to the cytocidal state. Hence, we also addressed the question whether or not Hb is able to activate macrophages in a similar manner. Our results were negative with regard to both questions. Further investigations indicated that, unlike the peroxidases, ferryl-Hb is unable to oxidize iodide to iodine at a measurable rate, which appears to be the reason for the lack of cytotoxic activity.