title: PEGylation is effective in reducing immunogenicity, immunotoxicity, and hepatotoxicity of α-momorcharin in vivo.
abstract: OBJECTIVE
  α-momorcharin (α-MMC), a type I ribosome-inactivating protein (RIP) from Momordica charantia, is well known for its antitumor and antivirus activities. However, the immunotoxicity and hepatotoxicity hampers its potential therapeutic usage. In order to reduce its toxicity, we had modified the α-MMC with polyethylene glycol (PEG), and detected the toxicity of the PEGylated α-MMC conjugates (α-MMC-PEG) in vivo.
  
  
  METHODS
  After α-MMC purified from bitter melon seeds, α-MMC-PEG was constructed with a branched 20 kDa (mPEG) 2-Lys-NHS, the tests of immunogenicity, immunotoxicity, and general toxicity of α-MMC-PEG were conducted in guinea pig and rat.
  
  
  RESULTS
  The titer of specific IgG in rats, immunized by α-MMC-PEG, were approximately one-third of those that by α-MMC, all the guinea pigs treated with α-MMC died of anaphylaxis shock within 5 min, while no animals treated with α-MMC-PEG died in the active systemic anaphylaxis (ASA) test. The passive cutaneous anaphylaxis (PCA) reaction of α-MMC-PEG challenge in rats was significantly smaller than that of the α-MMC. The liver damage was greatly released, such as the change of globulin (GLB), aspartate aminotransferase (AST), total bilirubin (TBIL) cholesterol (CHOL), albumin (ALB), and the degree of hepatocyte necrosis in repeated toxicity study.
  
  
  CONCLUSIONS
  PEGylation is effective in reducing the immunogenicity, immunotoxicity, and hepatotoxicity of α-MMC in vivo.
authors.affiliation: Department of Immunology, College of Preclinical and Forensic Medicine, Sichuan University, Chengdu, PR China.
authors.forename: Jue-cun
authors.initials: JC
authors.lastname: Zheng
authors.forename: Ning
authors.initials: N
authors.lastname: Lei
authors.forename: Qian-chuan
authors.initials: QC
authors.lastname: He
authors.forename: Wei
authors.initials: W
authors.lastname: Hu
authors.forename: Ja-Gui
authors.initials: JG
authors.lastname: Jin
authors.forename: Yao
authors.initials: Y
authors.lastname: Meng
authors.forename: Nian-hua
authors.initials: NH
authors.lastname: Deng
authors.forename: Yan-Fa
authors.initials: YF
authors.lastname: Meng
authors.forename: Chong-Jie
authors.initials: CJ
authors.lastname: Zhang
authors.forename: Fu-bing
authors.initials: FB
authors.lastname: Shen
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects / Q000737:chemistry* / Q000494:pharmacology*; D056486:Chemical and Drug Induced Liver Injury / Q000276:immunology / Q000473:pathology; D004354:Drug Screening Assays, Antitumor; D006168:Guinea Pigs; D022781:Hepatocytes / Q000276:immunology / Q000473:pathology; D007074:Immunoglobulin G / Q000276:immunology; D009336:Necrosis; D011092:Polyethylene Glycols / Q000009:adverse effects / Q000737:chemistry* / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D054788:Ribosome Inactivating Proteins / Q000009:adverse effects / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D007074:Immunoglobulin G; D011092:Polyethylene Glycols; C039582:MMC protein, Momordica charantia; D054788:Ribosome Inactivating Proteins