title: Alpha-momorcharin possessing high immunogenicity, immunotoxicity and hepatotoxicity in SD rats.
abstract: Momordica charantia L., a genus of Momordica Linn. of the family Cucurbitaceae, commonly known as bitter melon, has been widely planted in China, Southeast Asia, Turkey and other areas, and has been used as a medicine for a long time. Alpha-momorcharin (α-MMC) extracted and purified from bitter melon seeds has significant anti-tumor and anti-virus effects, and has potential toxicity as well, especially when taken overdose. However, up to date studies on its safety evaluation are still insufficient.
  
  
  OBJECTIVE
  The immunogenicity, immunotoxicity and general toxicity of α-MMC were investigated in rats and guinea-pigs, and the potential toxic effects of the agent on the body were also examined.
  
  
  METHODS
  The major ribosome-inactivating protein was isolated by column chromatographies from the protein extracted from bitter melon seeds, and was verified as α-MMC. After rats were immunized by α-MMC, titers of specific antibody to α-MMC in immunized rats serum were detected by indirect ELISA. Guinea-pigs and rats immunized with α-MMC were used to evaluate the active systemic anaphylaxis and passive cutaneous anaphylaxis induced by α-MMC relatively. α-MMC of 6.25 mg/kg, 2.08 mg/kg and 0.70 mg/kg was administered to rats every 2 days. Five weeks later, animals were sacrificed, and then, biochemical examination, analysis of bone marrow and peripheral blood cells, and histopathologic examination were performed.
  
  
  RESULTS
  The ribosome-inactivating protein isolated and purified from bitter melon seeds was identified as α-MMC. It induced high titer (1:46.4) of specific IgG and high positive results of the active systemic anaphylaxis and passive cutaneous anaphylaxis tests in animals. With the time of the α-MMC administration increasing, the body weights of the animals administered with α-MMC of 6.25 mg/kg decreased significantly, and point necrosis was also observed in liver cells, along with abnormal findings in serum chemistry, hematology and bone marrow histopathology test. The toxic effect lessened with the decrease of the dose of α-MMC and further reduced after the convalescence stage.
  
  
  CONCLUSIONS
  The results of the study show that α-MMC has high immunogenicity and immunotoxicity, and can cause obvious organic liver lesion.
authors.affiliation: West China Hospital Laboratory of Nanomedicine, Sichuan University, Chengdu, PR China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Meng
authors.forename: Bin
authors.initials: B
authors.lastname: Liu
authors.forename: Ning
authors.initials: N
authors.lastname: Lei
authors.forename: Juecun
authors.initials: J
authors.lastname: Zheng
authors.forename: Qianchuan
authors.initials: Q
authors.lastname: He
authors.forename: Dan
authors.initials: D
authors.lastname: Li
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Zhao
authors.forename: Fubing
authors.initials: F
authors.lastname: Shen
mesh_terms: D000707:Anaphylaxis / Q000139:chemically induced* / Q000276:immunology / Q000473:pathology; D000818:Animals; D000906:Antibodies / Q000097:blood; D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D001854:Bone Marrow Cells / Q000187:drug effects / Q000276:immunology; D001856:Bone Marrow Examination; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006168:Guinea Pigs; D008099:Liver / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008111:Liver Function Tests; D008297:Male; D020714:Maximum Tolerated Dose; D029777:Momordica charantia / Q000737:chemistry; D009336:Necrosis; D010323:Passive Cutaneous Anaphylaxis; D010936:Plant Extracts / Q000276:immunology / Q000302:isolation & purification / Q000633:toxicity*; D010946:Plants, Medicinal; D051381:Rats; D017207:Rats, Sprague-Dawley; D054788:Ribosome Inactivating Proteins / Q000276:immunology / Q000302:isolation & purification / Q000633:toxicity*; D012639:Seeds; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology; D013997:Time Factors; D018675:Toxicity Tests; D015431:Weight Loss / Q000187:drug effects
chemical_list: D000906:Antibodies; D015415:Biomarkers; D010936:Plant Extracts; C039582:MMC protein, Momordica charantia; D054788:Ribosome Inactivating Proteins