Preliminary Study Of Oxidative Stress Caused By Polymerized Hemoglobin And Intervention In Rats

Background:As the continuing lack of blood supply,the emergence of new virus transmitted from blood transfusion,the requirement of cross matching in blood transfusion,and other issues,blood substitutes were quickly developed.Hemoglobin-based oxygen carriers are a kind of blood substitutes,having the expansion ability and being able to carry and to release oxygen.It is easy to pass through the distal end of the damage blood vessels,alleviating the body hypoxia timely,and has a good effect in the treatment of acute anemia.However,the side effects of HBOCs,including oxidative stress,vasoactivity and gastrointestinal reaction restrict the development and commercialization.We have been engaged in the study of polymerized human placental hemoglobin(PolyPHb)for a long time,and previous study has demonstrated the efficacy of PolyPHb in rat shock model and blood exchange model.Therefore,based on the previous study,this study deeply investigates the oxidative stress induced by PolyPHb in rats and the intervention effect of vitamin C.Objective:Investigate the effect of low concentration of PolyPHb on oxidative stress in rats,and the intervention effect of vitamin C on oxidative stress caused by PolyPHb in rats.Methods:Establish the rat 70%blood exchange model,and divide the rats into NaCl group,(2%,4%,6%)PolyPHb group,2%PolyPHb +(0.025%,0.05%,0.1%)Vc group.Observe rat mean arterial pressure,heart rate and other physiological indexes before and after the blood replacement.After finishing the blood replacement,take arterial blood,measure the arterial blood gas.Then,separate plasma to detect Reduced Glutathione(GSH)concentration,Superoxide Dismutase(SOD)activity,Total antioxidant capacity(T-AOC),Methemoglobin(MetHb)concentration,Malondialdehyde(MDA)concentration,8-hydroxy-2 deoxyguanosine(8-OHDG)and vitamin C concentration to evaluate the level of oxidative stress in rats.Results:After 70%blood replacement,compared with NaCl group,SOD activity,GSH concentration,T-AOC,MetHb concentration,and MDA concentration in different concentrations of PolyPHb group were significantly increased(P<0.01),but the 8-OHDG concentration had no obvious change(P>0.05).After adding different concentrations Vc into 2%PolyPHb,low concentration Vc's SOD activity,GSH concentration,T-AOC,MetHb concentration,and MDA concentration had no obvious change(P>0.05),while middle and high concentration Vc's MDA concentration were significantly decreased(P<0.01).Conclusions:Infusion of low concentration PolyPHb can effectively alleviate oxidative stress in rats.In addition,PolyPHb can induce lipid peroxidation in rats,without DNA damage.High concentration VC can enhance the body antioxidant capacity and reduce lipid peroxidation in rats.