Derivatives Of Polyethylene Glycol Superoxide Dismutase And Its Metabolism In Vivo In New Zealand White Rabbits

Superoxide dismutase (SOD) is a kind of enzym ewhich can specially clear superoxide onion. It has important drug value with safety action on body, can widely apply for antitumorigenesis, radioresistance, anti-aging and anti-inflammatory. We modified SOD with a series of polyethylene glycol (PEG) and studied on stability of PEG-SOD. According to results we would know which kind of PEG is better. After this kind of PEG-SOD was fed on rabbits we studied whether it was absorbed by rabbits and studied on its metabolism in rabbits.SOD was modified by a series of PEG with cyanuric chloride method and modification ratio and activity remaining ratio of SOD were measured. PEG of low molecular weight had high modification ratio. PEG (MW6000) was better than others. Its modification ratio was 55.6% and activity remaining ratio was 85.4%.We studied on stability of PEG-SOD, including anti-acid, anti-alkali, anti-entymolysis abilities. It was found that PEG-SOD was more stable than native PEG-SOD (PEG6000) was better among them.125I-PEG-SOD(PEG6000) was prepared by chloine -T method and purified through G-50. The utilization ratio of 125I was 35.1%. The recovery ratio of protein was 69.1% .The specific radioactivity of 125I-PEG-SOD(PEG6000) was 1.37mCi/mg. Its radioactive chemical purity was identified by trichloroacetic acid deposit method and PAGE method, were 96.9?.55% and 96.5=0.89%(P>0.05), respectively. The activities of PEG-SOD (PEG6000) pre- and post-125I-lalel were measured. Two groups of data were compared. The result showed no statistically significant difference.The prototype of PEG-SOD (PEG6000) was detected by the method of 125I-labeI combined with PAGE. This method can meet the requirement of durg metabolism research in the specificity and sensitivity.After 125I-PEG-SOD(PEG6000) was fed on rabbits the prototype of it would be detected by the method of 125I-label combined with PAGE .The results showed the prototype of PEG-SOD (PEG6000)could be absorbed by intestinum tenue. The majority of it entered into plasma and the minority of it entered into enrythrocyte. At three hours after administration was fed blood concentration of the prototype of it reached its peak. The halflife time of PEG-SOD (PEG6000) in plasma was 7.8hr.We collected urine and feces of rabbits at 0~72hr after administration. The rate of excretion of overall radioactivity in urine and feces was 81.5%. The excretion of radioactivity in urine was 19.9% and the excretion of radioactivity in feces was 61.6%. There was no prototype of I125-PEG-SOD in urine assayed by PAGE and there was a small quantity prototype of it in feces.