Ferrous hemoglobin and hemoglobin‐based oxygen carriers acting as a peroxidase can inhibit oxidative damage to endothelial cells caused by hydrogen peroxide. Issue 10 (1st July 2021)

• Record Type: Journal Article
• Authors: Huo, Shuangshuang; Lei, Xiaofeng; He, Dan; Zhang, Hua; Yang, Zhipeng; Mu, Wenhua; Fang, Ke; Xue, Dan; Li, He; Li, Xiaoyan; Jia, Nan; Zhu, Hongli; Chen, Chao; Yan, Kunping
• Is Part Of: Artificial organs. Volume 45:Issue 10(2021)
• Page Start: 1229
• Page End: 1239
• Publication Date: 2021-07-01
• Subjects: catalysis -- ferrous Hb -- ferryl Hb -- hemoglobin‐based oxygen carriers -- peroxidase activity -- pseudoperoxidase cycle; Artificial organs -- Periodicals; 617.956
• DOI: 10.1111/aor.14009
• Languages: English
• ISSNs: 0160-564X

Abstract

Abstract: Oxidative damage caused by the ferryl hemoglobin is one of the major clinical adverse reactions of hemoglobin‐based oxygen carriers (HBOCs), while the production of reactive oxygen species in a pathological state can oxidize hemoglobin (HbFe 2+ ) to ferryl Hb, which can then enter the pseudoperoxidase cycle, making hemoglobin highly toxic. In this study, we found that ferrous hemoglobin and polymerized porcine hemoglobin (one of the HBOCs) have the peroxidase activity different from the pseudoperoxidase activity of ferric hemoglobin. Ferrous hemoglobin can catalyze the reaction of tyrosine (Tyr) with hydrogen peroxide. In addition, the results also indicated that ferrous hemoglobin and pPolyHb have a strong inhibitory effect on the pseudoperoxidase activity of ferric hemoglobin. Therefore, hydrogen peroxide was consumed in a large amount, which greatly prevented hemoglobin from becoming oxidized and entering the pseudoperoxidase cycle, thus inhibiting ferryl Hb toxicity. We further cultured human umbilical vein endothelial cells and monitored cell morphology, viability, cell cycle, apoptosis, lactate dehydrogenase (LDH) release, and malondialdehydes (MDAs) formation when incubated with H2 O2, Tyr, and HbFe 2+ . HbFe 2+ and pPolyHb reduced cell cycle arrest, apoptosis, LDH release, and MDA formation. These results showed that reducing oxidative damage induced by H2 O2 and converted hemoglobin from a molecule that is toxic to one that inhibits oxidative damage, suggesting a new strategy for development of a safer HBOCs. Abstract : Inhibition of the pseudoperoxidase cycle of ferryl‐ferric hemoglobin by peroxidase activity of HbFe 2+ . Driven by H2 O2, HbFe 2+ can be oxidized to HbFe 4+ and enter the pseudoperoxidase cycle of ferryl‐ferric hemoglobin. But after adding Tyr, HbFe 2+ can catalyze the reaction of Tyr with H2 O2 and prevent itself from being oxidized and entering the pseudoperoxidase cycle.