Alpha-momorcharin possessing high immunogenicity, immunotoxicity and hepatotoxicity in SD rats

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 (alpha-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. Aims of the study: The immunogenicity, immunotoxicity and general toxicity of alpha-MMC were investigated in rats and guinea-pigs, and the potential toxic effects of the agent on the body were also examined. Materials and methods: The major ribosome-inactivating protein was isolated by column chromatographies from the protein extracted from bitter melon seeds, and was verified as alpha-MMC. After rats were immunized by alpha-MMC, titers of specific antibody to alpha-MMC in immunized rats serum were detected by indirect ELISA. Guinea-pigs and rats immunized with alpha-MMC were used to evaluate the active systemic anaphylaxis and passive cutaneous anaphylaxis induced by alpha-MMC relatively. alpha-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 alpha-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 alpha-MMC administration increasing, the body weights of the animals administered with alpha-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 alpha-MMC and further reduced after the convalescence stage. Conclusions: The results of the study show that alpha-MMC has high immunogenicity and immunotoxicity, and can cause obvious organic liver lesion. (C) 2011 Elsevier Ireland Ltd. All rights reserved.