Effect of PEGylation of α-Momorcharin against Its Hepatotoxicity in Rats

JIN Jia-gui, MENG Yan-fa, GUO Wei, ZHENG Jue-cun, SHEN Fu-bing

Abstract

To explore the effect of PEGylation of α-Momorcharin (α-MMC), one of ribosome-inactivating proteins from bitter melon seed, against its hepatotoxicity in rats. Methods SD rats were randomized into NS group, α-MMC treated groups, and α-MMC-PEG treated groups. The doses of α-MMC and α-MMC-PEG were high, middle, and low dose(6.25, 2.08, 0.70 mg/kg). The rats were given different dose of α-MMC, or α-MMC-PEG via caudal vein every other day for consecutive 28 days and then left for 14 days recovery. The general condition of animals was observed, blood and liver samples were collected for liver function study and pathological examination on day 28 after initiation of administration and on day 14 after withdrawal. Results On day 28 after initiation of administration, the liver function damages were found in high-dose and middle-dose of α-MMC treated groups, such as the decreasing of ALB, increasing of GLB, A/G ratio decreasing and the dose-dependant increasing of AST, BIL and CHO. The pathological changes of hepatotoxicity were also observed in these two groups, including the massive hepatocyte, swelling degeneration, inflammatory cell infiltration, congestion and diffusive necrosis. However, the liver function and pathological changes in α-MMC-PEG treated groups were better than those in α-MMC treated groups. Conclusion PEGylation could reduce the hepatotoxicity of α-MMC to rats.

 

Keywords: α-Momorcharin, PEGylation, Rat hepatotoxicity

 

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References


Deans R. Abbott J. Review of intrauterine adhesions. J Minim Invasive Gynecol,2010; 17(5);555-569.

Kodaman PH, Arici A. Intra-uterine adhesions and fertility outcome; how to optimize success, Curr Opin Obstet Gynecol, 2007;19(3):207-214.

Robinson JK. Colimon LM, Isaacson KB. Postoperative adhesiolysis therapy for intrauterine adhesions ( Asherman’ s syndrome). Fertil Steril,2008;90(2) :409-414.

Hynes RO. The extracellular matrix: not just pretty fibrils. Science,2009;326(5957): 1216-1219.

Mariasegaram M, Tesch DH, Verhardt S, et al. Lefty antagonises TGF-£l induced epithelial-mesenchymal transition in tubular epithelial cells. Biochem Biophys Res Commun. 2010;393(4):855-859.

Hinz B. Tissue stiffness, latent TGF-1 activation, and mechanical signal transduction; implications for the pathogenesis and treatment of fibrosis. Curr Rheumatol Rep, 2009;11(2):120-126.

Wgster D, Zhu C, Bjrck HM, et al. Effects of PIXjF-C and PDGF-D on monocyte migration and MMP-2 and MMP-9 expression. Atherosclerosis,2009;202(2) :415-423.

Thomson AJ, Abbott JA, Kingston A, et al. Fluoroscopically guided synechiolysis for patients with Asherman' s syndrome: menstrual and fertility outcomes. Fertil Steril, 2007; 87 ( 2 ); 405-410.

Yu D. Li TC, Xia E, et al. Factors affecting reproductive outcome of hysteroscopic adhesiolysis for Asherman’ s syndrome. Fertil Steril,2008;89(3);715-724.

Pabuccu R. Onalan G. Kaya С, et al. Efficiency and pregnancy outcome of serial intrauterine device-guided hysteroscopic adhesiolysis of intrauterine synechiae. Fertil Steril, 2008; 90 (5):1973-1977.

Trappmann B, Gautrot JE. Connelly JT, et al. Extracellular- matrix tethering regulates stem-cell fate. Nat Mater, 2012; 11 (7) ;642-649.

Tashiro Y, Nishida C, Sato-Kusubata K. et al. Inhibition of PAI-1 induces neutrophil-driven neoangiogenesis and promotes tissue regeneration via production of angiocrine factors in mice. Blood,2012;119(26):6382-6393.

Aucella F, Margaglione M, Vigilante M, et al. PAI-1 4G/5G and ACE I/D gene polymorphisms and the occurrence of myocardial infarction in patients on intermittent dialysis. Nephrol Dial Transplant,2003; 18(6): 1142-1146.

Meltzer ME, Lisman T, de Groot PG, et al. Venous thrombosis risk associated with plasma hypofibrinolysis is explained by elevated plasma levels of TAFI and PAI-1. Blood. 2010;116(1) : 113-121.

Paolillo R. Iovene M, Romano CC, et al. Induction of VEGF and MMP-9 expression by toll-like receptor 2/4 in human endothelial cells infected with Chlamydia pneumoniae. Int J Immunopathol Pharmacol,2012;25(2);377-386.

Meng Y, Liu B, Lei N, et al. Alpha-momorcharin possessing high immunogenicity. immunotoxicity and hepatotoxicity in SD rats. J Ethnopharmacol.2012; 139(1):590-598.

Li ME, Chen YW, Liu ZY, et al. Anti-tumor activity and immunological modification of ribosome-inactivating protein (RIF) from Momordica charantia by covalent attachment of polyethylene glycol. Acta Bioch Bioph Sin, 2009; 41 ( 9); 792- 799.

Bian XX. Shen FB, Chen YW. et al. PEGylation of alpha- momorcharin: synthesis and characterization of novel anti-tumor conjugates with therapeutic potential. Biotechnol Lett, 2010;32(2);883-890.

Chapman AP. PEGylated antibodies and antibody fragments for improved therapy; a review. Adv Drug Del Rev» 2002; 54 (4);531-545.

Duncan R. The dawning era of polymer therapeutics. Nat Rev Drug Discov,2003;2(5):347-360.

Chan WY, Huang H, Tam SC. Receptor-mediated endocytosis of trichosanthin in choriocarcinoma cells. Toxicology,2003; 186 (2):191-203.

Zheng G, Baehinsky DR, Kovie IS, et al. Organ distribution in rats of two members of the low-density lipoprotein receptor gene family, gp330 and LRP/alpha 2MR, and the receptor- associated protein (RAP). J Histochem Cytochem, 1994; 42 (4):531-536.


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