Hongli Zhu

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

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.

Pharmacodynamic Study of Polymerized Porcine Hemoglobin (pPolyHb) in a Rat Model of Exchange Transfusion

Abstract: The objective of the present study is to evaluate the pharmacodynamic properties of polymerized porcine hemoglobin (pPolyHb) in an exchange transfusion model. Each of two groups of rats received a volume of pPolyHb or hetastarch that equalled 120–140% of estimated total blood volume (70 ml/kg) exchange transfusion. The results showed pPolyHb retained hemodynamic stability and exhibited superior volume expansion capability. Furthermore, pPolyHb effectively reverse anaerobic metabolism caused by a large amount of volume exchange. In comparison with hetastarch, pPolyHb increased blood oxygen content and tissue oxygenation. All these properties contribute to a higher effectiveness in sustaining the lives of rats in pPolyHb group.

Immune Safety Evaluation of Polymerized Porcine Hemoglobin (pPolyHb): A Potential Red Blood Cell Substitute

Abstract: Polymerized Porcine Hemoglobin (pPolyHb), a hemoglobin-based oxygen carrier (HBOC), was developed as a potential red blood substitute for clinical applications. Assessment of its effects on the immune system is an important component of the overall safety evaluation of HBOC. For this purpose, we assessed three inflammation indicators, including complement C3a, IL-6, and TNF-α in cultured cells and in a rat model when pPolyHb was incubated or administrated with the cells/animals. Our results suggested that the levels of these three indicators were not statistically changed upon pPolyHb stimulation, indicating that pPolyHb is not immunotoxic to cells and animals in this aspect.

Study of the effects of polymerized porcine hemoglobin (pPolyHb) in an acute anemia rat model

Abstract The objective of this study was to investigate the recovery ability of polymerized porcine hemoglobin (pPolyHb) in a rat model of acute anemia caused by normovolemic hemodilution (ANH). After the ANH procedure, rats were infused with either pPolyHb or red blood cells. The results showed pPolyHb could carry a sufficient amount of oxygen to the tissues to maintain normal aerobic metabolism and hemodynamic stability, without any significant toxic effects on renal and liver function according to pathological, and biochemical analysis. The data suggest pPolyHb may be a good candidate for the treatment of acute anemia in future clinical trials.

Effects of resuscitation with polymerized porcine hemoglobin (pPolyHb) on hemodynamic stability and oxygen delivery in a rat model of hemorrhagic shock.

Abstract The objective of this study was to evaluate the effects of polymerized porcine hemoglobin (pPolyHb) on hemodynamic stability and oxygen delivery in a rat model of hemorrhagic shock. Rats underwent controlled hemorrhage, resulting in the loss of 65% of their blood volume in 90 minutes. The results showed that pPolyHb was superior to hetastarch and saline, and similar to whole blood, in restoring hemodynamic stability and reversing anaerobic metabolism caused by hemorrhage. Furthermore, pPolyHb improved oxygen supply and increased blood oxygen content. These data suggest that pPolyHb can be effective in improving tissue perfusion under conditions of severe hemorrhagic shock.

The protective effect of polymerized porcine hemoglobin (pPolyHb) on transient focal cerebral ischemia/reperfusion injury.

Abstract Glutaraldehyde-polymerized porcine hemoglobin (pPolyHb) is a hemoglobin-based oxygen carrier currently being developed as a potential red blood cell substitute. We assessed the protective effect of pPolyHb on transient focal cerebral ischemia/reperfusion (I/R) injury. Several outcomes were tested, including infarct size, neurological score, production of inflammatory factors, and markers of oxidative status. Our results show that pPolyHb can not only significantly reduce infarct volume and improve neurological score, but can also inhibit the expression of TNF-α and IL-1β. Furthermore, the generation of MDA and MPO was reduced by pPolyHb. We conclude that pPolyHb has a positive effect on transient focal cerebral I/R injury.

Glutaraldehyde-polymerized hemoglobin and tempol (PolyHb-tempol) has superoxide dismutase activity that can attenuate oxidative stress on endothelial cells induced by superoxide anion

Abstract A Tempol compound with an amine group (4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl, NH2-Tempol) was cross-linked to hemoglobin in a one-step polymerization reaction to produce a novel hemoglobin-based oxygen carrier (HBOC) designated PolyHb-Tempol. The reaction parameters, including the reaction time, pH, temperature, and ratio of reactants, were optimized, and the physiochemical properties of the resulting product were characterized. PolyHb-Tempol didn’t show any toxicity towards endothelial cells. Furthermore, from observations of cell morphology and viability, PolyHb-Tempol showed a significant ability to inhibit or eliminate oxidative stress induced by superoxide free radicals. These results suggest that PolyHb-Tempol may potentially be suitable as an HBOC.

The effect of pPolyHb on hemodynamic stability and mesenteric microcirculation in a rat model of hemorrhagic shock

Abstract The effects of polymerized porcine hemoglobin (pPolyHb) on hemodynamic stability and maintenance of mesenteric microvascular function were explored in a rat model of hemorrhagic shock (HS). Following controlled hemorrhage, rats were infused with equal volumes of either pPolyHb, hetastarch (HES), or red blood cell (RBC). The results showed that pPolyHb was superior to HES and RBC in restoring hemodynamic stability and reversing anaerobic metabolism. We observed a reduction in the diameter of mesenteric microvasculature after HS. Resuscitation with pPolyHb and RBC was able to restore the diameters of the venules and arterioles, whereas HES failed to restore the diameters during the observation period.

Study of the inflammatory response of immunocytes to polymerized porcine hemoglobin (pPolyHb)

Polymerized porcine hemoglobin (pPolyHb), which was synthesized from chemically modified porcine hemoglobin, can carry and deliver oxygen to tissues in addition to restoring intravascular volume. Assessment of the inflammatory response generated in the host is a part of the overall safety evaluation of pPolyHb. In this study, we measured the levels of IL-1β, IL-10, and CD11b/CD18 in response to pPolyHb stimulation, both in vivo (in rats) and in vitro. Our results suggest that the levels of these indicators are not statistically changed by pPolyHb, indicating that pPolyHb is not immunotoxic to cells and animals in this respect.

The application of polymerized porcine hemoglobin (pPolyHb) in the rat small bowel preservation

Abstract Small bowel transplantation (SBTx) has become a standard clinical treatment for short bowel syndrome or irreversible intestinal function failure. Optimum preservation of the organ is essential for the success of transplantation. In this study, pPolyHb was used as an additive to hypertonic citrate adenine solution (HCA) to provide oxygen for rat small bowel transplant. Rat small bowels were preserved in HCA, HCA with pPolyHb, and University of Wisconsin solution (UW) for 12, 24, and 36 h, respectively. The results suggested that the preservation effect of HCA with pPolyHb was comparable with the UW solution, and more effective than the HCA solution.