A Novel Hemoglobin‐Based Oxygen Carrier, Polymerized Porcine Hemoglobin, Inhibits H₂O₂‐Induced Cytotoxicity of Endothelial Cells

Abstract

Hemoglobin-based oxygen carriers (HBOCs), with their capacity for delivering oxygen, could potentially function as red blood cell substitutes or primary resuscitation solutions. However, there has been some concern regarding redox-related safety issues of HBOCs. The present study describes a novel function of polymerized porcine hemoglobin (pPolyHb) in protecting a human umbilical vein endothelial cell line from H₂O₂-induced cytotoxicity. Through the examination of H₂O₂ consumption and ferrylhemoglobin formation, we found that pPolyHb exhibits antioxidant activity, suggesting that pPolyHb may protect cells from free radical-induced cell damage. Additionally, we investigated the effect of pPolyHb on H₂O₂-induced cell cytotoxicity, and found that pPolyHb significantly inhibits H₂O₂-mediated endothelial cell damage as well as apoptosis. Thus, pPolyHb may be developed as a new HBOC in the future.

Salidroside Inhibits Endogenous Hydrogen Peroxide Induced Cytotoxicity of Endothelial Cells

“…ROS, such as hydrogen peroxide, superoxide anion and hydroxyl radicals, readily damage biological molecules, which could ultimately lead to apoptosis or cell death. 15,16) Thus, protection of endothelial cells from ROS-induced injury may therefore provide beneficial therapeutical intervention for successful treatment of cardiovascular diseases. 17) Salidroside, a major active ingredient exsiting naturally in R. rosea L., has been reported to be a strong antioxidant.…”

Study on Oxidation Stability and Oxygen Affinity of Hemoglobin During Storage

“…HBOCs in practice were expected to maintain stability in long production and storage processes . However, in the absence of an antioxidant system, including superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) , the heme iron of Hb is easily oxidized to the ferric state (methemoglobin, metHb), which cannot carry oxygen . Therefore, research on oxidation is essential to improve the capability of Hb as an HBOC.…”

Artificial Oxygen Carriers—A Clinical Point of View

“…In this regard, transgenic mice were tested and found to be capable of antigen presentation against third‐party antigens in the presence of 20 mL/kg of LEH (15), suggesting the persistence of antigen‐presenting capability even after a large amount of LEH administration. Although new cell‐free HBOCs (6–8) have been proposed not for transfusion but for various other indications including the reduction of oxidative stress, their xenogeneic Hb remained to be tested for the absence of immunogenicity.…”

“…This may account at least in part for the nonlinear (23) or reversed U‐shaped dose‐response relationship (17,18) discussed earlier. Therefore, antioxidant effects (6–8,24) of AOCs may contribute to their benefits in pathological conditions involving tissue ischemia and reperfusion (22).…”

“…Although recent reports suggesting deterioration of donated blood after 2 weeks of storage (3) may propel quests for AOCs, the synthesis of human hemoglobin (Hb) remains far behind the efficiency of blood donation. Thus, human RBCs remain the source of human Hb as in the liposome‐encapsulated Hb (LEH), that is, Hb‐vesicle (4) or liposomal‐Hb (5) unless xenogeneic Hb is used to manufacture cell‐free Hb‐based oxygen carriers (HBOCs) (6–8). As other alternatives, modified myoglobin (9) or totally synthetic molecules (10) await development.…”