Cancer Cell Int. 2011 Oct 31;11(1):38. doi: 10.1186/1475-2867-11-38.

The chemopreventive effect of Ginkgo biloba and Silybum marianum extracts on hepatocarcinogenesis in rats.

Cancer cell international

Hala O El Mesallamy, Nadia S Metwally, Mahmoud S Soliman, Kawkab A Ahmed, Mai M Abdel Moaty

PMID: 22040519 PMCID: PMC3225333 DOI: 10.1186/1475-2867-11-38

Abstract

BACKGROUND/OBJECTIVE: This study was designed to evaluate the potential chemopreventive activities of Ginkgo biloba extract (EGb) and Silybum marianum extract (silymarin) against hepatocarcinogenesis induced by N-nitrosodiethylamine (NDEA) in rats.

METHODS: Rats were divided into 6 groups. Group 1 served as normal control rats. Group 2 animals were intragastrically administrated NDEA at a dose of 10 mg/kg five times a week for 12 weeks to induce hepatocellular carcinoma (HCC). Groups 3 and 4 animals were pretreated with silymarin and EGb respectively. Groups 5 and 6 animals were posttreated with silymarin and EGb respectively. The investigated parameters in serum are alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma glutamyltransferase (GGT) and vascular endothelial growth factor (VEGF). The investigated parameters in liver tissue are malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR) and comet assay parameters.

RESULTS: In NDEA group, MDA level was elevated with subsequent decrease in GSH level and SOD, GPx and GR activities. In addition, NDEA group revealed a significant increase in serum ALT, AST and GGT activities and VEGF level. Furthermore, NDEA administrated animals showed a marked increase in comet assay parameters. These biochemical alterations induced by NDEA were confirmed by the histopathological examination of rat livers intoxicated with NDEA that showed an obvious cellular damage and well differentiated HCC.In contrast, silymarin+NDEA treated groups (3&5) and EGb+NDEA treated groups (4&6) showed a significant decrease in MDA level and a significant increase in GSH content and SOD, GPx and GR activities compared to NDEA group. Silymarin and EGb also beneficially down-regulated the increase in serum ALT, AST, GGT activities and VEGF level induced by NDEA. In addition, silymarin and EGb significantly decreased comet assay parameters. Histopathological examination of rat livers treated with either silymarin or EGb exhibited an improvement in the liver architecture compared to NDEA group.

CONCLUSIONS: The obtained findings suggested that silymarin and EGb may have beneficial chemopreventive roles against hepatocarcinogenesis through their antioxidant, antiangiogenic and antigenotoxic activities.

References

1. Hepatology. 1996 Mar;23(3):455-64 - PubMed
2. Clin Exp Med. 2008 Dec;8(4):193-8 - PubMed
3. Chem Biol Interact. 2008 Jan 10;171(1):79-88 - PubMed
4. Phytomedicine. 2007 Feb;14(2-3):196-203 - PubMed
5. Occup Med. 1999 Oct-Dec;14(4):839-48 - PubMed
6. J Hepatol. 2002 Nov;37(5):620-4 - PubMed
7. Clin Chem. 1978 Jan;24(1):58-73 - PubMed
8. Integr Cancer Ther. 2007 Jun;6(2):130-45 - PubMed
9. Int J Biol Sci. 2009 Aug 11;5(6):549-57 - PubMed
10. J Clin Gastroenterol. 2001 Aug;33(2):123-6 - PubMed
11. Blood. 1989 Jan;73(1):334-9 - PubMed
12. Cancer Lett. 2008 Oct 8;269(2):352-62 - PubMed
13. Mol Cancer Ther. 2007 Dec;6(12 Pt 1):3248-55 - PubMed
14. J Lab Clin Med. 1967 Jul;70(1):158-69 - PubMed
15. Anal Biochem. 1976 May 7;72:248-54 - PubMed
16. Nat Rev Cancer. 2006 Sep;6(9):674-87 - PubMed
17. Life Sci. 2004 Apr 2;74(20):2467-78 - PubMed
18. Ecotoxicol Environ Saf. 1985 Feb;9(1):64-70 - PubMed
19. Biochem Biophys Res Commun. 1972 Jan 31;46(2):849-54 - PubMed
20. Pharmacol Ther. 1996;71(1-2):57-81 - PubMed
21. J Cell Mol Med. 2009 Aug;13(8B):2122-2130 - PubMed
22. Arch Surg. 1999 Dec;134(12):1325-31; discussion 1331-2 - PubMed
23. Comp Biochem Physiol C Pharmacol Toxicol Endocrinol. 1998 Feb;119(2):125-9 - PubMed
24. Mutagenesis. 2008 May;23(3):143-51 - PubMed
25. World J Gastroenterol. 2005 Sep 7;11(33):5193-8 - PubMed
26. Food Chem Toxicol. 2004 Oct;42(10):1687-93 - PubMed
27. Chem Biol Interact. 2006 Jun 10;161(2):104-14 - PubMed
28. Cell. 1998 Oct 30;95(3):365-77 - PubMed
29. Cancer Res. 1999 Jan 1;59(1):99-106 - PubMed
30. Biochem Med. 1984 Apr;31(2):217-27 - PubMed
31. Braz J Med Biol Res. 2010 Mar;43(3):242-8 - PubMed
32. Lancet. 2000 Mar 11;355(9207):887-91 - PubMed
33. Steroids. 1994 Jun;59(6):383-8 - PubMed
34. Adv Exp Med Biol. 1991;283:157-64 - PubMed
35. World J Gastroenterol. 2005 Dec 21;11(47):7391-400 - PubMed
36. Cardiovasc Res. 2001 Sep;51(4):773-83 - PubMed
37. Eur J Pharmacol. 2007 Apr 10;560(2-3):110-6 - PubMed
38. Exp Toxicol Pathol. 2003 Jul;55(1):17-9 - PubMed
39. Pak J Pharm Sci. 2010 Jan;23(1):15-20 - PubMed
40. Phytother Res. 2010 Jan;24(1):119-28 - PubMed
41. Anticancer Res. 2006 Nov-Dec;26(6B):4457-98 - PubMed
42. Cancer Res. 2008 Aug 15;68(16):6822-30 - PubMed
43. Methods Enzymol. 1994;234:462-75 - PubMed
44. Food Chem Toxicol. 2009 Nov;47(11):2716-22 - PubMed
45. Chem Biol Interact. 2008 May 9;173(1):32-42 - PubMed
46. J Lab Clin Med. 1963 May;61:882-8 - PubMed
47. Exp Eye Res. 2002 Oct;75(4):421-30 - PubMed
48. World J Gastroenterol. 2002 Oct;8(5):832-6 - PubMed
49. Exp Cell Res. 1988 Mar;175(1):184-91 - PubMed
50. J Cell Biochem. 1991 Nov;47(3):211-8 - PubMed
51. Biochem Biophys Res Commun. 2000 Sep 16;276(1):371-8 - PubMed
52. Curr Oncol. 2006 Feb;13(1):14-26 - PubMed
53. Scanning. 1996 Sep;18(6):407-16 - PubMed
54. Eur J Surg Oncol. 2001 Jun;27(4):396-403 - PubMed
55. Mutat Res. 1997 Oct 6;379(2):201-10 - PubMed
56. World J Gastroenterol. 2004 Jan;10(1):37-41 - PubMed
57. Yonsei Med J. 2004 Aug 31;45(4):703-10 - PubMed
58. Cancer Res. 2008 Mar 15;68(6):2033-42 - PubMed
59. J Clin Chem Clin Biochem. 1976 Sep;14(9):421-7 - PubMed
60. J Biol Chem. 1974 Nov 25;249(22):7130-9 - PubMed
61. Hum Exp Toxicol. 2011 Mar;30(3):209-16 - PubMed
62. J Trace Elem Med Biol. 2010 Jan;24(1):52-7 - PubMed
63. Liver Int. 2007 Apr;27(3):393-9 - PubMed

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