Antigenotoxic Effects of the Disulfide Compound Persicasulfide A (PSA) on Rat Lymphocytes Exposed to Oxidative Stress

Abstract

The antigenotoxic effect of persicasulfide A (PSA) from Ferula persica on DNA damage induced by hydrogen peroxide (H₂O₂) was evaluated using single cell gel electrophoresis (SCGE). PSA was extracted from F. persica, characterized by NMR and its antioxidant/antigenotoxic effects were investigated. The antigenotoxic effect of solutions containing either PSA (1, 10, 50, 100, 200, 300, 400 and 500 μM) or ascorbic acid (250, 500, 750 and 1000 μM) alone, or in the presence of H₂O₂ (25, 50, 100 and 200 μM) were tested on lymphocytes derived from the blood of healthy male Wistar rats (250 – 300 g) by using the comet assay. The degree of damage to DNA after exposure to different solutions was calculated based on the amount of DNA present in the tail compared to the total amounts of lymphocyte DNA. PSA did not show genotoxicity and caused a 50 % reduction in DNA damage induced by H₂O (EC₅₀ : 476.47 ± 67.46 μM). Compared to the EC₅₀ for ascorbic acid (1399.23 ± 205.21 μM), it was deduced that PSA was more effective than ascorbic acid in the prevention of oxidative damage to DNA.

Key words

Ferula persica - Apiaceae - antigenotoxicity - comet assay - persicasulfide A

References

• 1 Iranshahi M, Amin G R, Amini M, Shafiee A. Sulfur containing derivatives from Ferula persica var. latisecta. .  Phytochemistry. 2003;  63 965-6
• 2 Kajimoto T, Yahiro K, Nohara T. Sesquiterpenoid and disulphide derivatives from Ferula assa-foetida. .  Phytochemistry. 1989;  28 1761-3
• 3 Bagirov V Y, Gasanova R Y, Burma O I, Ban′kovskii A I. Coumarins of Ferula szovitsiana and F. persica. .  Chem Nat Compounds. 1977;  13 279-81
• 4 Afifi FU Abu-Irmaileh B. Herbal medicine in Jordan with special emphasis on less c,ommonly used medicinal herbs.  J Ethnopharmacol. 2000;  72 101-10
• 5 Zargari A. Medicinal plants. Tehran; Tehran University Press 1996: 596-8
• 6 Chung L Y. The antioxidant properties of garlic compounds: allyl cysteine, alliin, allicin, and allyl disulfide.  J Med Food. 2006;  9 205-13
• 7 Wiseman H, Kaur H, Halliwell B. DNA damage and cancer: measurement and mechanism.  Cancer Lett. 1995;  93 113-20
• 8 Hertog M G, Feskens E J, Hollman P C, Katan M B, Kromhout D. Dietary antioxidant flavonoids and risk of coronary heart disease: the Zutphen elderly study.  Lancet. 1993;  342 1007-11
• 9 Willcox J K, Ash S L, Catignani G L. Antioxidants and prevention of chronic disease.  Crit Rev Food Sci Nutr. 2004;  44 275-95
• 10 Mirjani R, Shahverdi A -R, Iranshahi M, Amin G, Shafiee A. Identification of antifungal compounds from Ferula persica var.  persica Pharm Biol. 2005;  43 293-5
• 11 Shahverdi A R, Saadat F, Khorramizadeh M R, Iranshahi M, Khoshayand M R. Two matrix metalloproteinases inhibitors from Ferula persica var. persica. .  Phytomedicine. 2006;  13 712-7
• 12 Altman S A, Randers L, Rao G. Comparison of trypan blue dye exclusion and fluorometric assays for mammalian cell viability determinations.  Biotechnol Prog. 1993;  9 671-4
• 13 Mosaffa F, Behravan J, Karimi G, Iranshahi M. Antigenotoxic effects of Satureja hortensis L. on rat lymphocytes exposed to oxidative stress.  Arch Pharm Res. 2006;  29 159-64
• 14 Noroozi M, Angerson W J, Lean M E. Effects of flavonoids and vitamin C on oxidative DNA damage to human lymphocytes.  Am J Clin Nutr. 1998;  67 1210-8
• 15 Yen G C, Chen H Y. Scavenging effect of various tea extracts on superoxide derived from the metabolism of mutagens.  Biosci Biotechnol Biochem. 1998;  62 1768-70
• 16 Belloir C, Singh V, Daurat C, Siess M H, Le Bon A M. Protective effects of garlic sulfur compounds against DNA damage induced by direct- and indirect-acting genotoxic agents in HepG2 cells.  Food Chem Toxicol. 2006;  44 827-34
• 17 Yen G C, Hung Y L, Hsieh C L. Protective effect of extracts of Mesona procumbens Hemsl. on DNA damage in human lymphocytes exposed to hydrogen peroxide and UV irradiation.  Food Chem Toxicol. 2000;  38 747-54
• 18 Wang J, Sun B, Cao Y, Song H, Tian Y. Inhibitory effect of wheat bran feruloyl oligosaccharides on oxidative DNA damage in human lymphocytes.  Food Chem. 2008;  109 129-36
• 19 Venturi M, Hambly R J, Glinghammar B, Rafter J J, Rowland I R. Genotoxic activity in human faecal water and the role of bile acids: a study using the alkaline comet assay.  Carcinogenesis. 1997;  18 2353-9
• 20 Green M H, Lowe J E, Waugh A P, Aldridge K E, Cole J, Arlett C F. Effect of diet and vitamin C on DNA strand breakage in freshly-isolated human white blood cells.  Mutat Res. 1994;  316 91-102
• 21 Anderson D, Yu T W, Phillips B J, Schmezer P. The effect of various antioxidants and other modifying agents on oxygen-radical-generated DNA damage in human lymphocytes in the comet assay.  Mutat Res. 1994;  307 261-71
• 22 Yen G -C, Duh P -D, Tsai H -L. Antioxidant and pro-oxidant properties of ascorbic acid and gallic acid.  Food Chem. 2002;  79 307-13
• 23 Nakatani N. Antioxidants in herbs of Okinawa island.  ACS Sym Ser. 2003;  859 166-75
• 24 Arranz N, Haza A I, Garcia A, Moller L, Rafter J, Morales P. Protective effects of organosulfur compounds towards N-nitrosamine-induced DNA damage in the single-cell gel electrophoresis (SCGE)/HepG2 assay.  Food Chem Toxicol. 2007;  45 1662-9
• 25 Yin M C, Hwang S W, Chan K C. Nonenzymatic antioxidant activity of four organosulfur compounds derived from garlic.  J Agric Food Chem. 2002;  50 6143-7
• 26 Gao X, Dinkova-Kostova A T, Talalay P. Powerful and prolonged protection of human retinal pigment epithelial cells, keratinocytes, and mouse leukemia cells against oxidative damage: the indirect antioxidant effects of sulforaphane.  Proc Natl Acad Sci USA. 2001;  98 15 221-6
• 27 Wu C C, Sheen L Y, Chen H W, Tsai S J, Lii C K. Effects of organosulfur compounds from garlic oil on the antioxidation system in rat liver and red blood cells.  Food Chem Toxicol. 2001;  39 563-9
• 28 Knowles L M, Milner J A. Diallyl disulfide induces ERK phosphorylation and alters gene expression profiles in human colon tumor cells.  J Nutr. 2003;  133 2901-6
• 29 Germain E, Auger J, Ginies C, Siess M H, Teyssier C. In vivo metabolism of diallyl disulphide in the rat: identification of two new metabolites.  Xenobiotica. 2002;  32 1127-38