An octapeptide fragment containing the heme moiety hemeoctapeptide (CHP) was prepared by peptic and tryptic digestion of yeast cytochrome c (Candida krusei). CHP was highly purified by chromatography and other methods by which any impurity due to pyrogenic and antigenic substances was completely excluded. Two different types of experimental hypoxia were employed in which a protective effect of CHP and its related compounds against the denaturation of cells and organelles due to oxygen deficiency was examined. First, hemorrhagic lipemia caused by hemic hypoxia was produced in rabbits by a consecutive bleeding for several days' duration. The animals which were given cytochrome c or CUP (1 mg/kg, daily, as a form of saline solution) intravenously showed less elevation of serum lipid levels than control animals treated with an equivalent volume of saline. Second, anoxic hypoxia was produced by the exposure of rats to simulated high altitude, which resulted in the disruption of lysosomes and in release of tissue enzymes such as acid phosphatase and transaminases into the circulatory system. In each experiment, 6 or 8 rats, which were injected with saline or drug solution intraperitoneally 15 minutes before the exposure, were placed in a well ventilated vacuum box and the atomospheric pressure was reduced and kept constant at the 300 Torr during the test period. Such changes in both tissue and serum enzyme levels were fairly well suppressed in the aimals pretreated with CHP (1 mg/kg). In addition to these biological data, histopathological and histochemical observations showed that tissue damages due to high altitude which were most apparent in the liver were limited when the animals were given CHP. It is suggested that the physiological function of externally given cytochrome c may be attributed to the biological activity of an effective intermediate such as CHP.
