Cytotoxic and Genotoxic Effects of Aqueous Extracts of Rosmarinus officinalis L., Lavandula stoechas L. and Tilia cordata Mill. on in vitro Human Peripheral Blood Lymphocytes

Tülay Aşkın Çelik; Özlem Sultan Aslantürk

doi:10.17776/csj.405629

TR EN

Rosmarinus officinalis L., Lavandula stoechas L. and Tilia cordata Mill. Sulu Ekstrelerinin in vitro İnsan Periferal Kan Lenfositleri Üzerindeki Sitotoksik ve Genotoksik Etkileri

Öz

Bu çalışmanın amacı Rosmarinus officinalis, Lavandula stoechas L. ve Tilia cordata Mill'den elde edilen sulu ekstrelerin (infüzyon ve dekoksiyon), insan periferal kan lenfositleri üzerindeki in vitro sitotoksik ve genotoksik etkisinin araştırılmasıdır.

Bu amaçla, 3 kadından alınan lenfositler, R. officinalis (1.5 ve 3 mg / ml), L. stoechas (0,4 ve 1,2 mg/ ml) ve T. cordata (1 mg / ml ve 3 mg / ml) sulu ekstreleri ile 48 saat süreyle muamele edilmiştir. Denemelerde PBS negatif kontrol olarak, Mitomisin C (MMC) (0,25 μg / ml) ise pozitif kontrol olarak kullanılmıştır. Ekstrelerin lenfositlerdeki sitotoksik etkisi, mitotik indeks hesaplanarak belirlenmiştir. Ayrıca, lenfositlerideki kromozom aberasyonları ve mikronukleus oluşumları da belirlenmiştir.

Deneyde kullanılan sulu ekstreler, kontrol gruplarına kıyasla konsantrasyon artışına bağlı olarak, periferal lenfosit hücrelerinde bölünmeyi önemli ölçüde azaltmıştır (p <0,01). Yine, metafazdaki hücrelerin sayısı da azalmıştır. Bu nedenle, periferal lenfositlerde kromozom incelemesi yapılamamıştır. Bununla birlikte, sulu ekstre muameleleri periferal lenfositlerde kontrol gruplarına kıyasla mikronukleus oluşumuna neden olmıuştur (p <0,01).

L. stoechas ve T. cordata'nın 3 mg / ml dekoksiyon ekstreleri, 48 saatlik muameleden sonra lenfositler üzerinde en yüksek sitotoksik etkiyi göstermiştir. En yüksek genotoksik etki ise 1.2 mg / ml L. stoechas dekoksiyon ekstresi ile muameleden sonra ortaya çıkmıştır.

Anahtar Kelimeler

Sitotoksik etki,genotoksik etki,insan periferal kan lenfositleri,Lavandula stoechas,Rosmarinus officinalis,Tilia cordata

References

[1]. Harvey A. L., Natural products in drug discovery, Drug Discov Today., 13 (19/20) (2008) 894-901.
[2]. Limem-Ben Amor I., Boubaker J., Ben Sgaier M., et al., Phytochemistry and biological activities of Phlomis species, J Ethnopharmacol., 125 (2009) 183-202.
[3]. Karamanoli K., Vokou D., Menkissoglu U., Constantinidou I. H., Bacterial colonization of phyllosphere of Mediterranean aromatic plants, J. Chem. Ecol., 26 (2000) 2035.
[4]. Ozcan K., Antioxidant activities of rosemary, sage, and sumac extracts and their combinations on stability of natural peanut oil.J. Med. Food., 6 (2003) 267-270.
[5]. Minnunni M., Wolleb U., Mueller O., Pfeifer A., Aeschbacher H.U., Natural antioxidants as inhibitors of oxygen species induced mutagenicity, Mutat. Res., 269 (1992) 193-200.
[6]. Faixova Z., Faix S., Biological effects of Rosemary (Rosmarinus officinalis L.) essential oil, Folia Veterinaria., 52 (3-4) (2008) 135-139.
[7]. Fernandez L. J., Zhi N., Aleson C. L., Perez A. J. A., Kur V., Antioxidant and antibacterial activities of natural extracts, application in beef meat balls, Meat Science., 69-3 (2005) 371-380.
[8]. Huang H.C., Huang C. Y., Lin-Shiau S. Y., Lin J. K., Ursolic acid inhibits IL-1beta or TNF-alpha-induced C6 glioma invasion through suppressing the association ZIP/p62 with PKC-zeta and downregulating the MMP-9 expression, Mol. Carcinog., 48 (2009) 517-531.

[9]. Gonzalo V., Molina S., González-Vallinas M., García-Risco M.R., Fornaril T., Reglero G., Ramírez de Molina A., Production of Supercritical Rosemary Extracts and their Effect on Tumor Progression, J.Supflu, 79 (2012) 101-108.
[10]. Assessment report on Tilia cordata Miller, Tilia platyphyllos Scop., Tilia x vulgaris Heyne or their mixtures, flos EMA/HMPC/337067/2011.
[11]. Blumenthal M., Busse W. R., Goldberg A., Gruenwald J., Hall, T.,Chance, W.R., Robert, S.R., Klein, S., editors. The Complete German Commission E Monographs. American Botanical Council, Austin Texas 1998, 163.
[12]. Blumenthal M., Goldberg A., Foster S., Herbal Medicine-Expanded Commission E Monographs. American Botanical Council, Integrative Medicine Communication, Boston, MA, 2000, pp. 240-243.
[13]. Thomson A., Healing plants (a modern herbal); Mc Graw Hill Book Company; London, England, 1987.
[14]. Davis P.H. (ed.), Flora of Turkey and the East Aegean Islands. Vol. 7. Edinburgh University Press, Edinburgh, 1992, pp. 947.
[15]. Gören A. C., Topçu G., Bilsel G., Bilsel M., Aydoğmuş Z., Pezzuto J. M., The chemical constituents and biological activity of essential oil of Lavandula stoechas ssp. Stoechas, Z. Naturforsch. 57c (2002) 797-800.
[16]. Hsu C.K., Chang C.T., Lu H.Y., Chung Y. C., Inhibitory effects of the water extracts of Lavendula sp. on mushroom tyrosinase activity, Food Chem. DOI: 10.1016/j.foodchem.2007.02.008.
[17]. Gamez M.J., Jimenez J., Risco S., Zarzuelo A., Hypoglycemic activity in various species of genus Lavandula. Part I: Lavandula stoechas L. and Lavandula multifida L. Pharmazie. 42 (1987) 706-707.
[18]. Baytop T., Therapy with Medicinal Plants in Turkey (Past and Present). 2nd Edition. Nobel Medical Publishers, 1999, Istanbul.
[19]. Gilani A.H., Aziz N., Khan M.N., Shaheen F., Jabeen Q., Siddiqui B. S., Herzig J. W., Ethnopharmacological evaluation of the anticonvulsant, sedative and antispazmodic activities of Lavandula stoechas L., J. Ethnopharmacol., 71 (2000) 161-167.
[20]. González-Coloma A., Delgado F., Rodilla J. M., Silva L., Sanz J., Burillo J., Chemical and biological profiles of Lavandula luisieri essential oils from western Iberia Peninsula populations, Biochem Syst Ecol., 39 (2011) 1-8.
[21]. Sosa S., Altinier G., Politi M., Braca A., Morelli I., Loggia D., Extracts and constituents of Lavandula multifida with topical anti-inflammatory activity, Phytomedicine., 12-4 (2005) 271-277.
[22]. Dob T., Dahmane D., Agli M., Chelghoum C., Essential oil composition of Lavandula stoechas from Algeria, Pharm Biol., 44 (2006) 60-64.
[23]. Upson T. M., Grayer R. J., Greenham J. R., Williams C. A., Al-Ghamdi F., Chen F.H., Leaf flavonoids as systematic characters in the genera Lavandula and Sabaudia, Biochem Syst Ecol., 28 (2000) 991-1007.
[24]. Carrano A.V., Natarajan A.T., International Commission for protection against environmental mutagens and carcinogens, Mutat Res., 204-3 (1988) 379-406.
[25]. Anderson D., Human biomonitoring, Mutat. Res., 204 (1988) 353-541.
[26]. Tucher J. D., Preston R. J., Chromosome Aberrations, Micronuclei, Aneuploidy, Sister Chromatid Exchanges, and Cancer Risk Assessment, Mutat Res., 365 (1-3) (1996) 147-159.
[27]. Hagmar L., Brøgger A., Hansteen I. L., Heim S., Högstedt B., Knudaen L., Lambert B., Linnainmaa K., Mitelman F., Nordenson I., Reuterwall C., Salomaa S., Skerfving S., Sorsa M., Cancer risk in human predicted by ıncreased levels of 69 chromosomal aberrations in lymphocytes: Nordic study group on the health risk of chromosome damage , Cancer Res., 54 (1994) 2919-2922.
[28]. Heddle J.A., Cimino M.C., Hayashi M., Romagna F., Shelby M.D., Tucker J.D., Vanparys P., Mac Gregor J. T., Micronuclei as an index of cytogenetic damage: past, present, and future, Environ. and Mol. Mutagen., 18 (1991) 277-291.
[29]. Fenech M., Biomarkers of genetic damage for cancer epidemiology, Toxicology, 181 (2002) 411-416.
[30]. Rojas E., Herrera L.A., Sordo M., Gonsebatt M.E., Montero R., Rodriguez R., Ostrosky-Wegman P., Mitotic index and cell proliferation kinetics for identification of antineoplastic activity, Anticancer Drugs, 4 -6 (1993) 637-640.
[31]. Gadano A. B., Gurni A.A., Carballo M.A., Argentine folk medicine: Genotoxic effects of Chenopodiaceae family, Journal of Ethnophamacology, 103 (2006) 246-251.
[32]. Bonassi S., Hagmar L., Strömberg U., Montagud A.H., Tinnerberg H., Forni A., Heikkilä P., Wanders S., Wilhardt P., Hansteen I.L., Knudsen L.E., Norppa H., Chromosomal aberrations in lymphocytes predict human cancer independently of exposure to carcinogens, Cancer Res., 60 (2000) 1619-1625.
[33]. Bonassi S., Znaor A., Norppa H., Hagmar L., Chromosomal aberrations and risk of cancer in humans: an epidemiologic perspective, Cytogenet. Genome Res., 104 (2004) 376-382.
[34]. Bonassi S., Ugolni D., Kirsch-Volders M., Strömberg U., Vermeulen R., Tucker J.D., Human population with cytogenetic biomarkers: review of the literature and future prospectives, Environ. and Mol. Mutagen., 45 (2005) 258-270.
[35]. Savage J. R. K., Update on target theory as applied to chromosomal aberrations, Env. Mol. Mutagen., 22 (1993) 198-207.
[36]. Evans H. J., Handbook of mutagenicity test procedures. In: Kilbey, B.J., Legator, M., Nichols, W. and Ramel, C. (Eds.), Human peripheral blood 63 lymphocytes for the analysis of chromosome aberrations in mutagen tests. Second edition, Elsevier Science Publishers, BV. 1984, pp. 405-427.
[37]. Rencüzoğulları E., Topaktaş M., The relationship between quantities of bromodeoxyuridine and human peripheral blood with determination of the best differential staining of sister chromatids using Chromosome Medium-B, Fen ve Mühendislik Bilimleri Dergisi, 5-3 (1991) 19-24.
[38]. Speit G., Haupter S., On the mechanism of differential giemsa staining of bromodeoxyuridine substituted chromosomes. II. differences between the demostration of sister chromatid differentiation and replication patterns, Hum. Gen., 70 (1985) 126-129.
[39]. Savage J.R., Classification and relationships of induced chromosomal structual changes, J Med Genet., 13-2 (1976) 103-122.
[40]. Tice R.R., Boucher R., Luke C.A., Shelby M.D., Comparative cytogenetic analysis of bone marrow damage induced in male B6C3F1 mice by multiple exposures to gaseous 1,3 butadiene, Environmental Mutagenesis, 9 (1997) 235-250.
[41]. Roncada T., Vicentini V.E.P., Mantovani M.S., Possible modulating actions of plant extracts on the chromosome breaking activity of MMC and Ara-C in human lymphocytes in vitro, Toxicology in vitro, 18 (2004) 617-622.
[42]. Fenech M., The in vitro micronucleus technique , Mutat Res., 455(1-2) (2000) 81-95.
[43]. Kirsch-Volders M., Sofuni T., Aardemac M., Albertini S., Eastmond D., Fenech M., Ishidate Jr. M., Kirchner S., Lorge E., Morita T., Norppa H., Surralles J., Vanhauwaert A., Wakata A., Report from the in vitro micronucleus assay working group, Mutat. Res., 540 (2003) 153-163.
[44]. Murray E.B., Edwards J.W., Micronuclei in peripheral lymphocytes and exfoliated urothelial cells of workers exposed to 4,4_-methylenebis-(2- chloroaniline) MOCA, Mutat. Res., 446 (1999) 175-180.
[45]. Amorin M.I., Mergler D., Bahia M.O., Dubeau H., Miranda D., Lebel J., Burdano R.R., Lucotte M., Cytogenetic damage related to low levels of methyl mercury contamination in the Brazilian Amazon, An. Acad. Bras. Cienc., 72 (2000) 497-507.
[46]. Thierens H., Vral A., Morthier R., Aousalahm B., De Ridderm L., Cytogenetic monitoring of hospital workers occupationally exposed to ionizing radiation using the micronucleus centromere assay, Mutagenesis., 15 (2000) 245-249.
[47]. Holland N., Bolognesi C., Kirsch-Volders, M, Bonassi S, Zeiger E, Knasmueller S, et al., The micronucleus assay in human buccal cells as a tool for biomonitoring DNA damage: the HUMN project perspective on current status and knowledge gaps, Mutat Res., 659(1–2) (2008) 93-108.
[48]. Jain A.K., Andsorbhoy R.K., Cytogenetical studies on the effects of some chlorinated pesticides. III. Concluding remarks, Cytologia (Tokyo), 53 (1988) 427-436
[49]. Eroğlu H.E., Aksoy A., Hamzaoğlu E., Budak U., Albayrak S., Cytogenetic effects of nine Helichrysum taxa in human lymphocytes culture, Cytotechnology., 59-1 (2009) 65-72.
[50]. Lazutka J.R., Mierauskien J., Slap G., Dedonyt V., Genotoxicity of dill (Anethum graveolens L.), peppermint (Mentha piperita L.) andpine (Pinus sylvestris L.) essential oils in human lymphocytes and Drosophila melanogaster, Food Chem. Toxicol., 39 (2001) 485-492.
[51]. Rencüzoğulları E., İla H.B., Kayraldız A., Diler S. B., Yavuz A., Arslan M., Kaya F. F., Topaktaş M., The mutagenic and anti-mutagenic effects of Ecballium elaterium fruit juice in human peripheral lymphocytes, Russian Journal of Genetics, 42-6 (2006), 623-627.
[52]. Barreiro Arcos M.L., Cremaschi G., Werner S., Coussio J., Ferraro G., Anesini C., Tilia cordata Mill. extracts and scopoletin (isolated compound): Differential cell growth effects on lymphocytes, Phytother. Res., 20 (2006) 34-40.
[53]. Krimat S., Dob T., Toumi M., Metiji H., Kesouri K., Chelghoum C., Evaluation of phytochemicals, antioxidant and cytotoxic activities of Lavandula antineae Maire endemic medicinal plant from Algeria, Informatics Journals, 6-3 (2014) https://doi.org/10.18311/ajprhc/2014/517.
[54]. Meyer B. N., Ferrigni N. R., Putnam J. E., Jacobsen L. B., Nichols D. E., McLaughlin J. L., Brine shrimp: a convenient general bioassay for active plant constituents, Planta Medica, 45 (1982) 31-34.
[55]. Cheung S., Tai J., Anti-proliferative and antioxidant properties of rosemary Rosmarinus officinalis, Oncol. Res., 1-7 (2007) 525-531.
[56]. Lopez-Bote C.J., Gray J. L., Gomaa E. A., Flegal C.J., Effect of dietary administration of oil extracts from rosemary and sage on lipid oxidation in broiler meat, Br. Poult. Scrl., 39 (1998) 235-240.
[57]. Karpinska M., Borowski J., Danowska-Oziewicz M., Antioxidative activity of rosemary extract in lipid fraction of minced meat balls during storage in a freezer, Nahrung, 44 (2000) 38-41.
[58]. Santos P.A.S.R., Avanço G.B., .Marcelino R.I.A, Janeiro V.M.C., Valaderes M.C., Machinski M., Assessment of Cytotoxic Activity of Rosemary (Rosmarinus officinalis L.), Turmeric (Curcuma longa L.), and Ginger (Zingiber officinale R.) Essential Oils in Cervical Cancer Cells (HeLa), The Scientific World Journal. 2016, ID 9273078, 8 pages
[59]. De Marco A., Romanelli M., Stazzı M.A., Vitagliano E., Induction of micronucleated cells in Vicia faba and Allium cepa root tips treated with NTA, Mutat. Res., 171 (1986) 145-148.
[60]. Williams G.M., Methods for evaluating chemical genotoxicity, Ann. Rev. Pharmocol. Toxicol., 29 (1989) 189-211.
[61]. Migliore L., Baraler B.E., Giorgelli F., Minnunni M., Scarpato R., Loprieno N., Genotoxicity of emthyglyoxal: cytogenetic damage in human lymhocytes in vitro and intestinal cells of mice, Carcin., 11- (1990), 1503-1507.
[62]. Capasso R., Cristinzio G., Evidente A., Scognamiglio F., Isolation spectroscopy and selective phytotoxic effects of polyphenols from vegetable waste water, Phytoch., 31-12 (1992): 4125-4128.
[63]. Heddle J.A., Hite M., Kirkhart B., Mavournin K., MacGregor J.T., Newell G.W., Salamone M.F., The induction of micronuclei as a measure of genotoxicity. A report of the US environmental protection agency gene tox program, Mutat. Res., 123 (1983) 61-118.
[64]. Ford J.H., Schultz C.J., Correll, A.T., Chromosome elimination in micronuclei: a common cause of hypoploidy, Am J Hum Genet., 43-5 (1988) 733-40.
[65]. Lindholm C., Norppa H., Hayashi M., Sorsa M., Induction of micronuclei and anaphase aberrations by cytochalasin B in human lymphocyte cultures, Mutat Res., 260-4 (1991) 369-75.
[66]. Ford J.H., Correll A.T., Chromosome errors at mitotic anaphase, Genome., 35-4 (1992) 702-5.
[67]. Albertini R.J., Anderson D., Douglas G.R., Hagmar L., Hemminki K., Merlo F., Natarajan A.T., Norppa H., Shuker D.E., Tıce R., Waters M.D., Aitio A., IPCS guidelines for the monitoring of genotoxic effects of carcinogens in humans. International Programme on Chemical Safety, 463- 2 (2000) 111-72.
[68]. Pastor S., Gutierrez S., Creus A., Xamena N., Piperakis S., Marcos R., Cytogenetic analysis of Greek farmers using the micronucleus assay in peripheral lymphocytes and buccal cells, Mutagenesis, 16-6 (2001) 539-45.
[69]. Norppa H., Falck G.C.M., What do human micronuclei contain?, Mutagenesis, 18-3 (2003) 221-233.
[70]. Ballardini M., Scarpato R., Kotwal G.J., Barale R., In vitro mutagenicity studies of the antiretrovirals AZT, didanosine, and 3TC and a plant antiviral extract secomet-V derived from the Trifolium species, Ann. N.Y.Acad. Sci., 1056 (2005) 303-310.
[71]. Aşkın Çelik T., Aslantürk Ö.S., Cytotoxic and genotoxic effects of Lavandula stoechas aqueous extracts, Biologia, 62-3 (2007) 292-296.
[72]. Waters M. D., Stack H.F., Jackson M.A., Genetic toxicology data in the evaluation of potential human environmental carcinogens, Mutat Res., 437-1 (1999) 21-49.
[73]. Hagmar L., Stromberg U., Bonassi S., Hansteen I.L., Knudsen L.E., Lindholm C et al., Impact of types of lymphocyte chromosomal aberrations on human cancer risk: results from Nordic and Italian cohorts, Cancer Res., 64-6 (2001) 2258-63.
[74]. Bonassi S., Abbondandolo A., Camurri L., Dal Prá L., De Ferrari M., Degrassi F., Forni A., Lamberti L., Lando C., Padovani P. et al., Are chromosome aberrations in circulating lymphocytes predictive of future cancer onset in humans? Preliminary results of an Italian cohort study , Cancer Genet Cytogenet., 79-2 (1995) 133-5.
[75]. Hagmar L., Bonassi S., Strömberg U., Brøgger A., Knudsen L.E., Norppa H., Reuterwall C., Chromosomal aberrations in lymphocytes predict human cancer: a report from the European Study Group on Cytogenetic Biomarkers and Health (ESCH), Cancer Res., 58-18 (1998) 4117-21.
[76]. Liou S.H., Lung J.C. Chen Y.H.,Yang T., Hsieh L.L., Chen C.J., Wu T.N., Increased chromosome-type chromosome aberration frequencies as biomarkers of cancer risk in a blackfoot endemic area, Cancer Res., 59-7 (1999) 1481-4.
[77]. Bonassi S., Hagmar L., Stromberg U, Montagud AH, Tinnerberg H. et al., Chromosomal aberrations in lymphocytes predict human cancer independently of exposure to carcinogens. European Study Group on Cytogenetic Biomarkers and Health, Cancer Res., 60-6 (2000) 1619-25.
[78]. Smerhovsky Z., Landa K., Rössner P., Brabec M., Zudova Z. et al., Risk of cancer in an occupationally exposed cohort with increased level of chromosomal aberrations, Environ Health Perspect., 109-1 (2001) 41-5.
[79]. Bonassi S., Norppa H., Ceppi M., Stromberg U., Vermeulen R., Znaor A. et al., Chromosomal aberration frequency in lymphocytes predicts the risk of cancer: results from a pooled cohort study of 22 358 subjects in 11 countries, Carcinogenesis, 29-6 (2008) 1178-83.
[80]. Anesini C., Werner S., Borda E., Effect of Tilia cordata flower on lymphocyte proliferation: participation of peripheral type benzodiazepine binding sites, Fitoterapia, 70 (1999) 361-367.
[81]. Manuele M.G., Ferraro G., Anesini C., Effect of Tilia x viridis flower extract on the proliferation of a lymphoma cell line and on normal murine lymphocytes: contribution of monoterpenes, especially limonene, Phytotherapy Research, 22 (2008)1520- 1526
[82]. Tantaoui-Elaraki A., Beraoud L., Inhibition of growth and aflatoxin production in Aspergillus parasiticus by essential oils of selected plant materials, J. Environ. Pathol. Toxicol. Oncol., 13-1 (1994) 67-72.

Details

Primary Language

English

Subjects

-

Journal Section

Research Article

Authors

Tülay Aşkın Çelik ^*

Özlem Sultan Aslantürk

Publication Date

March 16, 2018

Submission Date

July 7, 2017

Acceptance Date

November 30, 2017

Published in Issue

Year 1970 Volume: 39 Number: 1

DOI

https://doi.org/10.17776/csj.405629

IZ

https://izlik.org/JA44CS93WR

Cite

RIS / Bibtex

APA

Aşkın Çelik, T., & Aslantürk, Ö. S. (2018). Cytotoxic and Genotoxic Effects of Aqueous Extracts of Rosmarinus officinalis L., Lavandula stoechas L. and Tilia cordata Mill. on in vitro Human Peripheral Blood Lymphocytes. Cumhuriyet Science Journal, 39(1), 127-143. https://doi.org/10.17776/csj.405629

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Cytotoxic and Genotoxic Effects of Aqueous Extracts of Rosmarinus officinalis L., Lavandula stoechas L. and Tilia cordata Mill. on in vitro Human Peripheral Blood Lymphocytes

Rosmarinus officinalis L., Lavandula stoechas L. and Tilia cordata Mill. Sulu Ekstrelerinin in vitro İnsan Periferal Kan Lenfositleri Üzerindeki Sitotoksik ve Genotoksik Etkileri

Öz

Anahtar Kelimeler