Avaliação da atividade mutagênica e genotóxica de Ginkgo biloba L. pelo teste do micronúcleo em camundongos
DOI:
https://doi.org/10.5216/rbn.v3i2.2620Keywords:
camundongos, citotoxicidade, extrato Ginkgo biloba, mutagenicidade, teste do micronúcleo.Abstract
Ginkgo biloba L. is a medicinal plant widely used worldwide for the treatment of cerebral insufficiency, vascular diseases and various other illnesses. In the present study, the clastogenic and/or aneugenic activities of G. biloba L. leaf extract (EGB 761) were evaluated using mouse bone marrow micronucleus assay in polycromatic erythrocytes. Groups of five animals were treated with EGB 761 by gavage administration in doses of 50 mg/kg, 100 mg/kg, and 200 mg/kg. For all the doses, the micronucleated polycromatic erythrocytes frequency (MNPCE) was evaluated after 24 hours of treatment. The cytological preparation was carried out according to Heddle methodology. The cytotoxicity was evaluated by the relationship between the polycromatic and normocromatic frequency (EPC/ENC). The results indicated that EGb 761 did not provoke a significant increase of MNPCE (P>0.05) compared to the negative control group. Cytotoxicity was not observed in all concentrations utilized (P>0.01) compared to the negative control group. Thus, it can be suggested that EGb 761 did not present mutagenic nor cytotoxic effects under these experimental conditions.
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Ahlemeyer, B., D. Selke, C. Schaper, S. Klumpp & J. Krieglstein. 2001. Ginkgolic acids induce neuronal death and activate protein phosphatase type-2C. Eur. J. Pharmacol. 430: 1-7.
Amri, H., S.O. Ogwuegbu, N. Boujrad, K. Drieu & V. Papadoppoulos. 1996. In vivo regula- tion of the peripheral-type benzodiazepine receptor and glucocorticoid synthesis by the Ginkgo biloba extract EGb 761 and isolated ginkgolides Endocrinology 137: 5707-5718.
Bastianetto, S. & R. Quirion.2002. EGb 761 is a neuroprotective agent against beta-amyloid toxicity. Cell. Mol. Biol. 48: 693-697.
Boone, C.W., G.J. Kelloff & W.E. Malone. 1990. Identification of candidate cancer chemopreventive agents and their evaluation in animal models and human clinical trials: a review. Cancer Res. 50: 2-9.
Chen, B., J. Cai, S.S. Song, X. Wang & Z. Chen. 2005. Effects of Ginkgo biloba extract on cat- ion currents in rat ventricular myocytes. Life Sciences 76: 1111-1121.
Choy, W.N. 2001. Regulatory Genetic toxicology tests. In: Choy, W. N. (ed.), Genetic Toxicol- ogy and Cancer Risk Assessment, p. 93-113, Marcel Dekker, Inc, New York.
Cohen-Salmon, C., P. Venault, B. Martin, M.J. Raffalli-Sébille, M. Barkats, F. Clostre, M.C. Pardon, Y. Christen, & G. Chapouthier. 1997. Effects of Ginkgo biloba extract (EGb-761) on learning and possible actions on aging. J. Physiol. 91: 291-300.
Cordell, G.A. 1995. Changing strategies in natural products chemistry. Phytochemistry 40: 1585-1612.
Couzinier, J.P. & S. Mamatas. 1986. Basic and applied research in the pharmaceutical industry into natural substances, p. 57-61. In: D. Barton, Ollis, W.D. (Eds), Advances in Medicinal Phytochemistry. John Libbey Montrouge, Eurotext.
De Feudis, F.V. 2003. A brief history of EGb 761 and its therapeutic uses. Pharmacopsychiatry. 36: 52-57.
De Feudis, F.V. 1998. Ginkgo biloba extract (EGb 761) from chemistry to the clinic. Wiesbaden, Ulstein Medical.
De Smet, P.A. 1995. Should herbal medicine-like products be licensed as medicines? Brit. Med. J. 310: 1023-1024.
Gaudineau, C.R. Beckerman & S. Welbourn, Auclair, K. 2004. Inhibition of human P450 enzymes by multiple constituents of the Ginkgo biloba extract. Bioch. Bioph. Res. Comm. 318: 1072-1078.
Elovic, E.P. & R.D. Zafonte. 2001. Ginkgo biloba: applications in traumatic brain injury. J. Head Trauma Rehabil. 16: 603-607.
Heddle, J.A. 1973. A rapid in vitro test for chromosomal damage. Mutat. Res. 18: 187-190.
Jaggy, H. & E. Koch. 1997. The chemistry and biology of alkyphenols from Ginkgo biloba L. Pharmazie 10: 735-738.
Kleijnen, J. & P. Knipschild. 1992. Ginkgo biloba for cerebral insufficiency. Br. J. Clin. Pharmac. 34: 352-358.
Koch, E., H. Jaggy, S.S Chatterjee. 2000. Evidence for immunotoxic effects of crude Ginkgo biloba L. leaf extracts using poplital lymph node assay in the mouse. Int. J. Immunopharmacol. 22: 229-236.
Kunitomo, M., K. Shinozuka, K. Umegaki, Y. Kubota, N. Tanaka, H. Mizuno, J. Yamauchi, K. Nakamura & M. Kunitomo. 2002. Feeding of Ginkgo biloba extract (GBE) enhances gene expression of hepatic cytochrome P-450 and attenuates the hypotensive effect of nicardipine in rats. Life Sciences 70: 2783-2792.
Oken, B.S., D.M. Storzbach & J.A. Kaye. 1998. The efficacy of Ginkgo biloba on cognitive function on Alzheimer’s disease. Arch. Neurol. 55: 1409-1415.
Pereira, D.G. 1999. Avaliação do potencial mutagênico e/ou recombinogênico de Hyptidendron canun (pohl ex Benth) R. Harley em células germinativas e somáticas de Drosophila melanogaster. Dissertação de Mestrado, Universidade Federal de Goiás, Goiânia.
Porsolt, R.D., P. Martin, A. Lenegre, S. Fromage & K. Drieu. 1990. Effects of an extract of Ginkgo biloba on “learned helplessness” and other models of stress in rodents. Pharmacol. Biochem. Behav. 36: 963-971.
Rapin, J.R., I. Lamproglou, K. Drieu & F.V. De Feudis. 1994. Demonstration of the “antistress” activity of an extract of Ginkgo biloba using a discrimination learning task. Gen. Pharmacol. 25: 1009-1016.
Rioufol, G., S. Pietri, M. Culcasi, J. Loufoua, P. Staat, C. Pop, K. Drieu & M. Ovise. 2003. Ginkgo biloba extract EGb 761 attenuates myocardial stunning in the pig heart. Basic Res. Cardiol. 98: 59-68.
Saller, R., J. Reichling & O. Kristof. 1998. Phytotherapie Behandlung ohne Ne-benwirkungen? Dtsch. Med. Wschr. 123: 58-62.
Schmid,W. 1975. The micronucleus test. Mutat. Res. 31: 9-15.
Seiichi, S. & T. Isao. 2001. Short-term scre-ening method of the prediction for the prediction of carcinogenicity of chemical substances: current status and problems of an in vivo rodent micronucleus assay. J. Health Sci. 47: 1-8.
Shaw, D., C. Leon, S. Kolev & V. Murray. 1997. Traditional remedies and food supplements. A 5-year toxicological study (1991-1995).
Drug Safety 17: 342-356.
Siegers, C.P. 1999. Cytotoxicity of alkylphenols from Ginkgo biloba. Phytomedicine 6: 281- 283.
Thiagaraja, G., S. Chandani, S.H. Rao, A.M. Samuni, K. Chandrasekaran & D. Bala-subramanian. 2002. Molecular and cellular assessment of Ginkgo biloba extract as a possible ophthalmic drug. Exp. Eye Res. 75: 421-430.
Wadsworth, T.L. & D.R. Koop. 2001. Effects of Ginkgo biloba extract (EGb 761) and quercetin on lipopolysaccharide-induced release of nitric oxide. Chem.-Biol. Interactions 137: 43-58.
Westendorf, J. & J. Regan. 2000. Genotoxic and tumor promoting activity of ginkgolic acids in primary rat hepatocytes. Phytomedicine 7 (Suppl. II): 104.
Zhao, H.W. & X.Y. Li. 2002. Ginkgolide A, B, and huperzine A inhibit nitric oxide-induced neurotoxicity. Int. Immunopharmacol. 2: 1551-1556.
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