TY - JOUR
T1 - Methemoglobin formation in hemoglobin vesicles and reduction by encapsukated thiols
AU - Takeoka, Shinji
AU - Sakai, Hiromi
AU - Kose, Takehiro
AU - Mano, Yuichi
AU - Seino, Yuriko
AU - Nishide, Hiroyuki
AU - Tsuchida, Eishun
PY - 1997
Y1 - 1997
N2 - The hemoglobin vesicle (HbV) is a red cell substitute encapsulating purified concentrated Hb in a phospholipid vesicle. In order to suppress metHb formation or autoxidation, for the long-term maintenance of the oxygen transporting capability, a series of thiols (cysteine, Cys; glutathione, GSH; homocysteine, Hcy; and acetylcysteine, Acy) were studied as reductants of metHb. Hcy and GSH showed a good suppressive effect on metHb formation, while Cys adversely accelerates the metHb formation at a rate twice that of the Hb solution without any reductants and Acy showed no change. The significant suppression by the coaddition of superoxide dismutase (SOD) and catalase to Cys indicated that Cys was easily oxidized by oxygen and simultaneously generates a large amount of active oxygens. The effective suppression of metHb formation by SOD and catalase was not observed for HbV containing no reductants, indicating that the generation of active oxygens from Hb itself is not significant. The coencapsulation of Hcy with Hb resulted in a low rate of metHb formation in HbV (initial rate, 1%/h) in vitro at oxygen partial pressure (P(O2)) of 142 Torr. The rate increased with decreasing P(O2), showed a maximum (2.2%/h) around P(O2) = 23 Torr, and then decreased to 0%/h at 0 Torr. From these results, it is suggested that the fast metHb formation rate in the blood circulation of Wistar rats injected with 20 vol % of the HbV solution would be mainly caused by the exposure of HbV to the low P(O2).
AB - The hemoglobin vesicle (HbV) is a red cell substitute encapsulating purified concentrated Hb in a phospholipid vesicle. In order to suppress metHb formation or autoxidation, for the long-term maintenance of the oxygen transporting capability, a series of thiols (cysteine, Cys; glutathione, GSH; homocysteine, Hcy; and acetylcysteine, Acy) were studied as reductants of metHb. Hcy and GSH showed a good suppressive effect on metHb formation, while Cys adversely accelerates the metHb formation at a rate twice that of the Hb solution without any reductants and Acy showed no change. The significant suppression by the coaddition of superoxide dismutase (SOD) and catalase to Cys indicated that Cys was easily oxidized by oxygen and simultaneously generates a large amount of active oxygens. The effective suppression of metHb formation by SOD and catalase was not observed for HbV containing no reductants, indicating that the generation of active oxygens from Hb itself is not significant. The coencapsulation of Hcy with Hb resulted in a low rate of metHb formation in HbV (initial rate, 1%/h) in vitro at oxygen partial pressure (P(O2)) of 142 Torr. The rate increased with decreasing P(O2), showed a maximum (2.2%/h) around P(O2) = 23 Torr, and then decreased to 0%/h at 0 Torr. From these results, it is suggested that the fast metHb formation rate in the blood circulation of Wistar rats injected with 20 vol % of the HbV solution would be mainly caused by the exposure of HbV to the low P(O2).
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U2 - 10.1021/bc970091y
DO - 10.1021/bc970091y
M3 - Article
C2 - 9258453
AN - SCOPUS:0031193434
VL - 8
SP - 539
EP - 544
JO - Bioconjugate Chemistry
JF - Bioconjugate Chemistry
SN - 1043-1802
IS - 4
ER -