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The inhibitory effects of garlic and Panax ginseng extract standardized with ginsenoside Rg3 on the genotoxicity, biochemical, and histological changes induced by ethylenediaminetetraacetic acid in male rats

  • Genotoxicity and Carcinogenicity
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Abstract

Ethylenediaminetetraacetic acid (EDTA) is widely used in food and other industries to sequester metal ions and to prevent their disadvantageous effects. The objective of the current study was to evaluate the protective effect of Panax ginseng extract standardized with ginsenoside Rg3 (ginsenoside Rg3 content was 3.6% w/w, i.e., 36 μg/mg P. ginseng extract) and garlic against EDTA-induced biochemical, genotoxic, and histological changes in rats. Forty male rats were divided into eight treatment groups and treated for 7 days as follows: the control group, the group treated with EDTA (20 mg/kg b.w) and the groups treated with P. ginseng extract (20 mg/kg b.w), garlic (5 mg/kg b.w), P. ginseng plus garlic alone or in combination with EDTA. In vivo bone marrow micronucleus test and random amplified polymorphism DNA-PCR (RAPD-PCR) method were performed to assess the antigenotoxic effect of both protective agents. The results indicated that EDTA administration caused a significant decrease in the serum biochemical parameters and antioxidant enzymes activity. The administration also increased lipid peroxidation and the incidence of micronucleated polychromatic erythrocytes (MnPCEs), caused appearance of some changes in polymorphism band patterns, and induced different histopathological lesions in the livers, kidneys, and testis. Treatment with P. ginseng, garlic alone or plus EDTA significantly improved all the tested parameters. Moreover, P. ginseng extract was found to be more effective than garlic in restoring the parameters that were altered by EDTA.

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References

  • Abdel-Wahhab MA, Ahmed HH (2004) Protective effects of Korean panax ginseng against chromium VI toxicity and free radical generation in rats. J Ginseng Res 28:11–17

    Article  CAS  Google Scholar 

  • Abdel-Wahhab MA, Aly SE (2003) Antioxidants and radical scavenging properties of vegetable extracts in rats fed aflatoxin-contaminated diet. J Agric Food Chem 51:2409–2414

    Article  PubMed  CAS  Google Scholar 

  • Abdel-Wahhab MA, Amer HA, Hassan NS, Hassan AM, Naguib K (2002) Effects of garlic and cabbage extracts on fimonisin-induced toxicity in rats. J Egypt Soc Toxicol 26:1–12

    Google Scholar 

  • Abdel-Wahhab MA, Hassan AM, Amer HA, Naguib KM (2004) Prevention of fumonisin-induced maternal and developmental toxicity in rats by certain plant extracts. J Appl Toxicol 24:469–474

    Article  PubMed  CAS  Google Scholar 

  • Abdel-Wahhab MA, Aly SE (2005) Antioxidant property of Nigella sativa (black cumin) and Syzygium aromaticum (clove) in rats during aflatoxicosis. J Appl Toxicol 25:218–223

    Article  PubMed  CAS  Google Scholar 

  • Abraham SK, Kesavan PC (1984) Genotoxicity of garlic, turmeric and asafoetida in mice. Mutat Res 136:85–88

    Article  PubMed  CAS  Google Scholar 

  • Adler ID (1984) Cytogenetic tests in mammals. In: Venitt S, Parry JM (eds) Mutagenicity testing (a practical approach). IRI Press, Oxford, pp 275–306

    Google Scholar 

  • Aquardo CF, Noom WA, Begun SJ (1992) RFLP analysis using heterologous probes. In: Hoelzel AR (ed) Molecular genetic analysis of populations, a practical approach. IRL press, Oxford, pp 115–157

    Google Scholar 

  • Arivazhagan S, Balasenthil S, Nagini S (2000) Modulatory effects of garlic and neem leaf extract on N-methyl-NV-nitro-N-nitrosoguanidine induced oxidative stress in Wistar rats. Cell Biochem Funct 18:17–21

    Article  PubMed  CAS  Google Scholar 

  • Arivazhagan S, Nagini S, Santhiya ST, Ramesh A (2001) Protection of N-methyl-NV-nitro-N-nitrosoguanidine-induced in vivo clastogenicity by aqueous garlic extract. Asia Pac J Clin Nutr 10:238–241

    Article  PubMed  CAS  Google Scholar 

  • Ashby J, DeSerres FJ, Shelby MD, Margolin BH, Ishidate MJR, Becking GC (1988) Evaluation of short-term tests for Carsinogens: report of the international programme on chemical safety’s collaborative study on in vivo assays. Cambridge University Press, Cambridge

    Google Scholar 

  • Bancroft D, Stevens A, Turner R (1996) Theory and practice of histological techniques, 4th edn. Churchill Livingstone, Edinburgh, London, Melbourne

    Google Scholar 

  • Bartles H, Bohmer M, Heirli C (1972) Serum creatinine determi-nation without protein preciptation. Clin Chem Acta 37:193–197

    Article  Google Scholar 

  • Basrur VR, Baker DG (1963) Human chromosome breakage in low-calcium cultures. Lancet i:1106–1107

    Article  Google Scholar 

  • Chandra Mohan KVP, Bhuvaneswari V, Abraham SK, Nagini S (2003) Dose-dependent protection by tomato against 7,12-dimethylbenz[a]anthracene-induced genotoxicity and oxidative stress in mice. J Med Food 6:169–173

    Article  PubMed  CAS  Google Scholar 

  • Doumas BT, Watson WA, Bigga HG (1971) Albumin standards and the measurement of serum albumin with bromacresal green. Clin Chem Acta 31:87–90

    Article  CAS  Google Scholar 

  • Duncan MG (1999) The effects of nutritional supplements on treatment of depression, diabetes and hypercholesterolemia in the renal patient. J Ren Nutr 9:58–62

    Article  PubMed  CAS  Google Scholar 

  • Esterbauger H, Schaure RJ, Zollner H (1991) Chemistry and biochemistry of 40 hydroxy-nonenal malonaldehyde and related aldehydes. Free Radiol Biol Med 11:81–128

    Article  Google Scholar 

  • Fishbein L, Flamm WG, Falk HL (1970) Chemical mutagens; environmental effects on biological systems. Academic, New York, pp 249–251

    Google Scholar 

  • Fukuda S (1987) Assessment of the carcinogenic hazard of 6 substances used in dental practice. Part I. Morphological transformation, DNA damage and sister chromatid exchanges in cultured Syrian hamster embryo cells induced by carbol camphor, eugenol, thymol, EDTA, benzalkonium chloride and benzethonium chloride. Odontology 74:1365–1384

    PubMed  CAS  Google Scholar 

  • Gao Y, Xu J, Sun B, Jiang H (2002) Microencapsulated hepatocytes and islets as in vivo bioartificial liver support system. World J Gastroenteral 10:2067–2071

    Google Scholar 

  • Grass GM, Robinson JR (1988) Mechanisms of corneal drug penetration. In: in vivo and in vitro kinetics. J Pharm Sci 77:3–14

    Google Scholar 

  • Grass GM, Wood RW, Robinson JR (1985) Effects of calcium chelating agents on corneal permeability. Invest Ophthalmol His Sci 26:110–113

    CAS  Google Scholar 

  • Hagiwara M, Watanabe E, Barrett JC, Tsutsui T (2006) Assessment of genotoxicity of 14 chemical agents used in dental practice: ability to induce chromosome aberrations in Syrian hamster embryo cells. Mutat Res 603:111–120

    PubMed  CAS  Google Scholar 

  • Heimbach J, Rieth S, Mohamedshah F, Slesinski R, Samuel-Fernando P, Sheehan T, Dickmann R, Borzelleca J (2000) Safety assessment of iron EDTA [sodium iron (Fe3+) ethylenediaminetetraacetic acid]: summary of toxicological, fortification and exposure data. Food Chem Toxicol 38:99–111

    PubMed  CAS  Google Scholar 

  • Heindorff K, Aurich O, Michaelis A, Rieger R (1983) Genetic toxicology of ethylenediaminetetraacetic acid (EDTA). Mutat Res 115:149–173

    PubMed  CAS  Google Scholar 

  • Henry JB, Sanford T, Davidsohn A (1974) clinical diagnosis and measurement by laboratory methods, 16th edn. Saunders WB, Philadelphia, PA, pp 260–265

    Google Scholar 

  • INACG (1993) Iron EDTA for food fortification. A report of the international nutritional anemia consultative group. The Nutrition Foundation Inc., Washington, DC

    Google Scholar 

  • Ivanova T, Han Y, Son HJ, Yun YS, Song JY (2006) Antimutagenic effect of polysaccharide ginsan extracted from Panax ginseng. Food Chem Toxicol 44:517–521

    Article  PubMed  CAS  Google Scholar 

  • JECFA (1974) Toxicological evaluation of some food additives including anticaking agents, antimicrobials, antioxidants, emulsifiers and thickening agents. Joint FAO/WHO Expert Committee on Food Additives. WHO Tech Rep Ser No. 539

  • JECFA (1993b) Toxicological evaluation of certain food additives and contaminants. WHO food additive series 32. Joint FAO/WHO expert committee on food additives. IPCS, World Health Organization, Geneva

    Google Scholar 

  • JECFA (1993c) Evaluation of certain food additives and contaminants. WHO technical report series 837. 41st report of the joint FAO/WHO expert committee on food additives. World Health Organization, Geneva

    Google Scholar 

  • Jonkers D, Vandenbroek E, Vandooren I, Thijs C, Dorant E, Hageman G, Stobberingh E (1999) Antibacterial effect of garlic and omeprazole on Helicobacter pylori. J Antimicrob Chemother 43:837–839

    Article  PubMed  CAS  Google Scholar 

  • Kakizoe T (2000) Asian studies of cancer chemoprevention: latest clinical results. Europ J Cancer 36:1303–1309

    Article  CAS  Google Scholar 

  • Kampen JV, Robertson H, Hagg T, Drobitch R (2003) Neuroprotective actions of the ginseng extract G115 in two rodent models of Parkinson’s disease. Exp Neuro 184:521–529

    Article  Google Scholar 

  • Kik C, Kahane R, Gebhardt R (2001) Garlic and health. Nut Metab Cardiovas Dis 11:57–65

    CAS  Google Scholar 

  • Kim HJ, Chun YJ, Park JD, Kim SI, Roh JK, Jeong TC (1997) Protection of rat liver microsomes against carbon tetrachloride-induced lipid peroxidation by red ginseng saponin through cytochrome P450 inhibition. Planta Med 63:415–418

    Article  PubMed  CAS  Google Scholar 

  • Kumaraguruparan R, Chandra Mohan KVP, Abraham SK, Nagini S (2005) Attenuation of N-methyl-NV-nitro-N-nitrosoguanidine induced genotoxicity and oxidative stress by tomato and garlic combination. Life Sci 76:2247–2255

    Article  PubMed  CAS  Google Scholar 

  • Lee BM, Lee SK, Kim HS (1998) Inhibition of oxidative DNA damage, 8-OHdG, and carbonyl contents in smokers treated with antioxidants (vitamin E, vitamin C, β-carotene and red ginseng). Cancer Lett 132:219–227

    Article  PubMed  CAS  Google Scholar 

  • Lee YJ, Pantuck CB, Pantuck EJ (1993) Effect of ginseng on plasma levels of ethanol in the rat. Planta Med 59:17–19

    Article  PubMed  CAS  Google Scholar 

  • Lerner P, Milbert A, Beloian A, Hattan DG (1986) A review of the current position of the us food and drug administration on EDTA compounds, including sodium iron EDTA. center for food safety and applied nutrition. US Food and Drug Administration, Washington, DC

    Google Scholar 

  • Lin CC, Hsu YF, Lin TC, Hsu FL, Hsu HY (1998) Antioxidant and hepatoprotective aactivity of punicalagin and punicalin on carbon tetrachloride-induced liver damage in rats. J Pharm Pharmacol 50:789–794

    PubMed  CAS  Google Scholar 

  • Loo WTY, Cheung MNB, Chow LWC (2004) The inhibitory effect of a herbal formula comprising ginseng and carthamus tinctorius on breast cancer. Life Sci 76:191–200

    Article  PubMed  CAS  Google Scholar 

  • Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Vhem 193:265–275

    CAS  Google Scholar 

  • Luceri C, De Filippo C, Caderni G, Gambacciani L, Salvadori M, Giannini A, Dolara P (2000) Detection of somatic DNA alterations in azoxymethane-induced F344 rat colon tumors by random amplified polymorphic DNA analysis. Carcinogenesis 21:1753–1756

    Article  PubMed  CAS  Google Scholar 

  • Manna GK, Das RK (1976) Conjpoint effects of EDTA and MH (maleic hydrazide) on the frequency of chromosome aberrations in mice. Chromosome Information Service 20:28–29

    Google Scholar 

  • Mannaa F, Abdel-Wahhab MA, Ahmed HH, Park MH (2006) Protective role of panax ginseng extract standardized with ginsenoside Rg3 against acrylamide-induced neurotoxicity in rats. J Appl Toxicol 26:198–206

    Article  PubMed  CAS  Google Scholar 

  • Muralidhara A, Narasimhamurthy K (1991) Assessment of in vivo mutagenic potency of ethylenediaminetetraacetic acid in albino mice. Food Chem Toxicol 29:845–849

    Article  PubMed  CAS  Google Scholar 

  • Ogundele MO (1998) The role of divalent cations in the mechanisms of EDTA Cytotoxicity. Presented at INABIS ‘98–5th Internet world congress on biomedical sciences at McMaster University, Canada, Dec 7–16

  • Paglia DE, Valentine WN (1967) Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J Lab Clin Med 70:158–169

    PubMed  CAS  Google Scholar 

  • Panwar M, Kumar M, Samarth R, Kumar A (2005) Evaluation of chemopreventive action and antimutagenic effect of the standardized panax ginseng extract, EFLA400, in swiss albino mice. Phytother Res 19:65–71

    Article  PubMed  CAS  Google Scholar 

  • Reuber MD, Schmieller GC (1962) Edetate lesions in rats. Arch Environ Health 5:430–436

    PubMed  CAS  Google Scholar 

  • Salvati G, Genovesi G, Marcellini L, Paolini P, De Nuccio I, Pepe M, Re M (1996) Effects of panax Ginseng C.A. Meyer saponins on male fertility. Panminerva Med 38:249–254

    PubMed  CAS  Google Scholar 

  • Sambrook L, Fritsch EF, Manitatis T (1989) Molecular cloning: a laboratory manual. Cold Spring Harbor Press, Cold Spring Harbor, NY

    Google Scholar 

  • SAS (1982) SAS user’s guide: statistics, 1982 edn. SAS Institute Inc., Cary, NC

    Google Scholar 

  • Shukla Y, Taneja P (2002) Antimutagenic effects of garlic extract on chromosomal aberrations. Cancer Lett 176:31–36

    Article  PubMed  CAS  Google Scholar 

  • Siegers CP, Steffen B, Robke A, Pentz R (1999) The effects of garlic preparations against human tumor cell proliferation. Phytomedicine 6:7–11

    PubMed  CAS  Google Scholar 

  • Suttle NF (1986) Copper deficiency in ruminants, recent developments. The Vet Rec 119:519–522

    CAS  Google Scholar 

  • Siu PI, Duncan HFM, Pui CL, Michel KTP, Kam MK (1996) Effect of a lignan-enriched extract of Scisandra chinensis on aflatoxin B1 and cadmium chloride- induced hepatotoxity in rats. Pharmacol Toxicol 78:413–416

    Article  Google Scholar 

  • Tadi PP, Teel RW, Lau BHS (1991) Organosulfur compounds of garlic modulate mutagenesis, metabolism, and DNA binding of aflatoxin B1. Nutr Cancer 15:87–95

    Article  PubMed  CAS  Google Scholar 

  • Taylor DM, Jones JD (1972) Effects of ethylenediaminetetraacetate and diethylenetriaminepentaacetate on DNA. Synthesis in kidney and intestinal mucosa of folate treated rats. Biochem Pharmacol 21:3313–3315

    Article  PubMed  CAS  Google Scholar 

  • Tietz NW (1987) Fundamentals of clinical chemistry, 2nd edn. Saunders, Philadelphia, PA, p 657

    Google Scholar 

  • Wang H, Ma X, Deng Q, Li D (2002) Cytotoxicity of flutamide and 2-hydroxyflutamide and their effects on CYP1A2 mRNA in primary rat hepatocytes. Acta Pharmacol Sin 23:562–566

    PubMed  CAS  Google Scholar 

  • Weisburger JH (2002) Lycopene and tomato products in health promotion. Exp Biol Med 227:924–927

    CAS  Google Scholar 

  • Wang H, Wei W, Shen Y, Domg C, Zhang L, Wang N, Yue L, Xu S (2004) Protective effect of melatonin against liver injury in mice induced by Bacillus Calmette Guerin plus Lipopolysccharide. World J Gastroenteral 10:2690–2696

    CAS  Google Scholar 

  • Zhang D, Yasuda T, Yu Y, Zheng P, Kawabata T, Ma Y, Okada S (1996) Ginseng extract scavenges hydroxyl radical and protects unsaturated fatty acids from decomposition caused by iron-mediated lipid peroxidation. Free Radic Biol Med 20:145–150

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Cell Biology Department, National Research Center, Dokki, Cairo, Egypt

    Wagdy K. B. Khalil

  2. Pathology Department, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt

    Kawkab A. Ahmed

  3. Ambo Institute, Seoul, South Korea

    Myung H. Park

  4. Lotte R&D Center, Lotte Group, Seoul, 150-964, South Korea

    Yong T. Kim & Hyung H. Park

  5. Food Toxicology and Contaminants Department, National Research Center, Dokki, Cairo, Egypt

    Mosaad A. Abdel-Wahhab

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  1. Wagdy K. B. Khalil
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  2. Kawkab A. Ahmed
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  3. Myung H. Park
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  6. Mosaad A. Abdel-Wahhab
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Correspondence to Mosaad A. Abdel-Wahhab.

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Khalil, W.K.B., Ahmed, K.A., Park, M.H. et al. The inhibitory effects of garlic and Panax ginseng extract standardized with ginsenoside Rg3 on the genotoxicity, biochemical, and histological changes induced by ethylenediaminetetraacetic acid in male rats. Arch Toxicol 82, 183–195 (2008). https://doi.org/10.1007/s00204-007-0237-y

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