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Planta Med 2009; 75(1): 37-40
DOI: 10.1055/s-0028-1088341
Pharmacology
Original Paper
© Georg Thieme Verlag KG Stuttgart · New York

Genotoxicity Evaluation of Three Benzopyrans from Hypericum polyanthemum

Alexandre de Barros Falcão Ferraz1 , Juliana da Silva1 , Luiz Irineu Deimlimg1 , Renato Santos-Mello1 , Andrea Sharlau1 , Gilsane L. von Poser2 , Jaqueline Nascimento Picada1
  • 1Programa de Pós-graduação em Genética e Toxicologia Aplicada, Universidade Luterana do Brazil, Canoas, RS, Brazil
  • 2Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil
Further Information

Publication History

Received: May 30, 2008 Revised: August 28, 2008

Accepted: September 25, 2008

Publication Date:
07 November 2008 (online)

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Abstract

In the present study we used the micronuclei test and the comet assay in mice to investigate the genotoxic and mutagenic effects of three benzopyrans – 6-isobutyryl-5,7-dimethoxy-2,2-dimethyl-benzopyran (HP1); 7-hydroxy-6-isobutyryl-5-methoxy-2,2-dimethyl-benzopyran (HP2); and 5-hydroxy-6-isobutyryl-7-methoxy-2,2-dimethyl-benzopyran (HP3) – isolated from Hypericum polyanthemum. No significant difference in polychromatic erythrocyte (PCE) percentage between the vehicle group and groups treated with HP1, HP2, or HP3 was detected, indicating no toxicity to the bone marrow of the animals. Only HP1 increased the frequency of micronucleated cells (MNPCEs) in bone marrow sampled after 24 h in comparison with the vehicle group, suggesting a weak mutagenic effect. The damage index and damage frequency did not show a significant increase after treatment with HP1, HP2, or HP3 in comparison with the vehicle group. The antitumor activity previously reported in vitro for these benzopyrans, the lack of acute toxicity, the MN induction only for HP1, and the relatively low DNA damage make all compounds good candidates for in vivo studies on antitumor action.

Key words

benzopyrans - Hypericum polyanthemum - Clusiaceae - comet assay - micronuclei test

References

  • 1 Viana A F, Heckler A P, Fenner R, Rates S MK. Antinociceptive activity of Hypericum caprifoliatum and Hypericum polyanthemum (Guttiferae).  Braz J Med Biol Res. 2003;  36 631-4
    PubMedSearch in Google Scholar
  • 2 Ribeiro V L, Toigo E, Bordignon S A, Gonçalves K, von Poser G. Acaricidal properties of extracts from the aerial parts of Hypericum polyanthemum on the cattle tick Boophilus microplus. .  Vet Parasitol. 2007;  147 99-203
    PubMedSearch in Google Scholar
  • 3 Dall’ Agnol R, Ferraz A, Bernardi A P, Albring D, Nör C, Sarmento L. et al . Antimicrobial activity of some Hypericum species.  Phytomedicine. 2003;  10 511-6
    CrossrefPubMedSearch in Google Scholar
  • 4 Ferraz A, Faria D H, Benneti M N, Brondani da Rocha A, Schwartsmann G, Henriques A. et al . Screening for antiproliferative activity of six southern Brazilian species of Hypericum. .  Phytomedicine. 2005;  12 112-5
    CrossrefPubMedSearch in Google Scholar
  • 5 Ferraz A BF, Bordignon S AL, Staats C, Schripsema J, von Poser G L. Benzopyrans from Hypericum polyanthemum. .  Phytochemistry. 2001;  57 1227-30
    CrossrefPubMedSearch in Google Scholar
  • 6 Sato A, Shindo T, Kasanuki N, Hasegawa K. Antioxidant metabolites from the tunicate Amaroucium multiplicatum. .  J Nat Prod. 1989;  52 975-81
    CrossrefPubMedSearch in Google Scholar
  • 7 Isman M B, Proksch P, Yan J Y. Insecticidal chromenes from the Asteraceae: structure-activity relations.  Entomol Exp Appl. 1987;  43 87-93
    CrossrefPubMedSearch in Google Scholar
  • 8 Agarwal S K, Verma S, Singh S S, Tripathi A K, Khan Z K, Kumar S. Antifeedant and antifungal activity of chromene compounds isolated from Blepharispermum subsessile. .  J Ethnopharmacol. 2000;  71 231-4
    CrossrefPubMedSearch in Google Scholar
  • 9 Boonlaksiri C, Oonanant W, Kongsaeree P, Kittakoop P, Tanticharoen M, Thebtaranonth Y. An antimalarial stilbene from Artocarpus integer. .  Phytochemistry. 2000;  54 415-7
    CrossrefPubMedSearch in Google Scholar
  • 10 Parmer T G, Ward M D, Hait W N. Effects of rottlerin, an inhibitor of calmodulin-dependent protein kinase III, on cellular proliferation, viability, and cell cycle distribution in malignant glioma cells.  Cell Growth Differ. 1997;  8 327-34
    PubMedSearch in Google Scholar
  • 11 Gnerre C, von Poser G L, Ferraz A, Viana A, Testa B, Rates S MK. Monoamine oxidase inhibitory activity of some Hypericum species native to South Brazil.  J Pharm Pharmacol. 2001;  53 1273-9
    CrossrefPubMedSearch in Google Scholar
  • 12 Dall’Agnol R, Ferraz A, Bernardi A P, Albring A, Nor C, Schapoval E ES. et al . Bioassay-guided isolation of antimicrobial benzopyrans and phloroglucinol derivatives from Hypericum species.  Phytother Res. 2005;  19 291-3
    CrossrefPubMedSearch in Google Scholar
  • 13 Ferraz A BF, Grivicich I, von Poser G L, Faria D H, Kayser G B, Schwartsmann G. et al . Antitumor activity of three benzopyrans isolated from Hypericum polyanthemum.  Fitoterapia. 2005;  76 210-5
    CrossrefPubMedSearch in Google Scholar
  • 14 OECD. Organization for Economic Co-operation and Development. Mammalian Erythrocyte Micronuclei Test. Guideline for the Testing of Chemicals. Updated Test Guideline 474. Paris, France; Available online for a fee at http://www.oecd.org// ehs/test/health.htm # ADOPTED GUIDELINES Accessed 2008
    Search in Google Scholar
  • 15 Miller B, Potter L F, Seelbach A, Stopper H, Utesch D, Madle S. Evaluation of the in vitro micronuclei test as an alternative to the in vitro chromosomal aberration assay: position of the GUM Working Group on the in vitro micronuclei test. Gesellschaft fur Umwelt-Mutations-forschung.  Mutat Res. 1998;  410 81-116
    PubMedSearch in Google Scholar
  • 16 Schmidt W. The micronuclei test.  Mutat Res. 1975;  31 9-15
    PubMedSearch in Google Scholar
  • 17 Santos-Mello R, Deimlimg L I, Lauer Jr C M, Almeida A. Induction of micronuclei by alkaloids extracted from Senecio brasiliensis and stored for 23 years.  Mutat Res. 2002;  516 23-8
    PubMedSearch in Google Scholar
  • 18 Singh N P, McCoy M T, Tice R R, Scheneider E L. A simple technique for quantitation of low levels of DNA damage in individual cells.  Exp Cell Res. 1988;  175 184-91
    CrossrefPubMedSearch in Google Scholar
  • 19 Silva J, Freitas T RO, Marinho J R, Speit G, Erdtmann B. An alkaline single-cell gel electrophoresis (comet) assay for environmental biomonitoring with native rodents.  Genet Mol Biol. 2000;  23 241-5
    PubMedSearch in Google Scholar
  • 20 Nadin S B, Vargas-Roig M L, Ciocca D R. A silver staining for singlecell gel assay.  J Histochem Cytochem. 2001;  49 1183-6
    PubMedSearch in Google Scholar
  • 21 Picada J N, Flores D G, Zettler C G, Marroni N P, Roesler R, Henriques J AP. DNA damage in brain cells of mice treated with an oxidized form of apomorphine.  Mol Brain Res. 2003;  114 80-5
    CrossrefPubMedSearch in Google Scholar
  • 22 Duddy S K, Stephen Hsia M T. Alteration of precocene II-induced hepatotoxicity by modulation of hepatic glutathione levels.  Chem Biol Interact. 1989;  71 187-99
    CrossrefPubMedSearch in Google Scholar
  • 23 Halpin R A, Vyas K P, El-Naggar S F, Jerina D M. Metabolism and hepatotoxicity of the naturally occurring benzo[b]pyran precocene I.  Chem Biol Interact. 1984;  48 297-315
    CrossrefPubMedSearch in Google Scholar
  • 24 Picada J N, da Silva K VCL, Erdtmann B, Henriques A T, Henriques JA P. Genotoxic effects of structurally related β-carboline alkaloids.  Mutat Res. 1997;  379 135-49
    PubMedSearch in Google Scholar
  • 25 Tice R R, Agurell E, Anderson D, Burlinson B, Hartmann A, Kobayashi H. et al . Single cell gel/comet assay: guidelines for in vitro and in vivo genetic toxicology testing.  Environ Mol Mutagen. 2000;  35 206-21
    CrossrefPubMedSearch in Google Scholar
  • 26 Yehoyada M B, Gautier J, Dupré A. The DNA damage response during an unperturbed S-phase.  DNA Repair. 2007;  6 914-22
    CrossrefPubMedSearch in Google Scholar
  • 27 Bonassi S, Au W W. Biomarkers in molecular epidemiology studies for health risk prediction.  Mutat Res. 2002;  511 73-86
    PubMedSearch in Google Scholar

Prof. Dr. Alexandre de Barros Falcão Ferraz

Programa de Pós-graduação em Genética e Toxicologia Aplicada

Universidade Luterana do Brazil

Av. Farroupilha

8001 Canoas RS

Brazil

Phone: +51-3477-9214

Fax: +51-3477-9239

Email: alexandre.ferraz@ulbra.br