The Effect of Human Recombinant Superoxide Dismutase Conjugated with Polyethylene Glycol on the Hepatic Toxicity of Acetaminophen

HrSOD-폴리에칠렌 접합체의 아세트아미노펜 간독성에 미치는 영향

  • Yong, Chul-Soon (College of Pharmacology, Yeungnam University) ;
  • Park, Kyong-Ah (College of Pharmacology, Yeungnam University) ;
  • Oh, Doo-Man (College of Pharmacology, Catholic University of Taegu-Hyosung)
  • 용철순 (영남대학교 약학대학) ;
  • 박경아 (영남대학교 약학대학) ;
  • 오두만 (대구효성가톨릭대학교 약학대학)
  • Published : 1995.12.20

Abstract

The covalent conjugation of human recombinant superoxide dismutase (hrSOD) with trichloros-triazine activated polyethylene glycol (PEG) 5000 formed soluble conjugates with molecular weight of 92KD, which retained $90{\sim}98%$ of original activity with a markedly prolonged plasma half-life of enzyme activity. The effect of hrSOD-PEG conjugates on acetaminophen (ACP)-induced hepatotoxicity was tested in male rats which were pretreated with 3-methylcholanthrene. HrSOD-PEG conjugates inhibited the hepatotoxicity produced by ACP, on the other hand, native hrSOD had no protective effect. The above results indicated that oxygen radicals might participate in the mechanism of the ACP-induced hepatotoxicity and that polymer conjugated-protein drugs with prolonged half-lives could be employed as an effective therapeutic agent.

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