Hydroxytyrosol: lack of clastogenicity in a bone marrow chromosome aberration study in rats

BMC Research Notes

Nicole Amann¹  Hana Hofman-Hüther³  Laurie C Dolan² 

[1] Wacker Chemie AG, Johannes-Hess-Str. 24, Burghausen 84489, Germany;Burdock Group, 859 Outer Road, Orlando, FL 32814, USA;Department of in vitro Pharmacology/Toxicology, BSL BIOSERVICE Scientific Laboratories GmbH, Behringstr. 6/8, 82152, Planegg, Munich, Germany

关键词: Chromosome aberration;    Rat;    Hydroxytyrosol;   

Others  :  1091694
DOI  :  10.1186/1756-0500-7-923

 received in 2014-09-09, accepted in 2014-12-12,  发布年份 2014

【 摘 要 】

Background

Hydroxytyrosol is naturally found in olives, olive oil and wine, and is consumed as part of a normal diet. The substance may have utility as a preservative in a wide variety of foods due to its antioxidant, antimicrobial and amphipathic properties. The potential for hydroxytyrosol to cause chromosome aberrations in vitro had been tested previously, with positive results at high concentrations. An OECD Guideline 475 study (mammalian bone marrow chromosome aberration test) was conducted in rats with the oral limit dose of 2000 mg/kg bw to determine whether hydroxytyrosol is a clastogen in vivo.

Results

The oral limit dose of 2000 mg/kg hydroxytyrosol was well tolerated by most rats; however, some rats exhibited clinical signs that abated within 24 hours. Treatment with hydroxytyrosol did not significantly enhance the number of aberrant cells or the mitotic index 24 or 48 hours post-dose. The positive control (cyclophosphamide) induced the expected increase in chromosomal aberrations and a decrease in the mitotic index, confirming the validity of the assay.

Conclusion

An oral limit dose of 2000 mg/kg hydroxytyrosol does not induce chromosome aberrations in bone marrow cells of the rat. Accordingly, hydroxytyrosol is not a clastogen in vivo.

【 授权许可】

   
2014 Dolan et al.; licensee BioMed Central.

【 图 表 】

Figure 1.

【 参考文献 】

• [1]Blekas G, Vassilakis C, Harizanis C, Tsimidou M, Boskou DG: Biophenols in table olives. J Agric Food Chem 2002, 50:3688-3692.
• [2]Shenoy SF, Chowanadisai W, Sharman E, Keen CL, Liu J, Rucker RB: Biofactors in food promote health by enhancing mitochondrial function. Calif Agric 2011, 65:141-147.
• [3]Papadopoulos G, Boskou D: Antioxidant effect of natural phenols on olive oil. J Am Oil Chem Soc 1991, 68:669-671.
• [4]Visioli F, Bellomo G, Galli C: Free radical-scavenging properties of olive oil polyphenols. Biochem Biophys Res Commun 1998, 247:60-64.
• [5]Bisignano G, Tomaino A, Lo Cascio R, Crisafi G, Uccella N, Saija A: On the in-vitro antimicrobial activity of oleuropein and hydroxytyrosol. J Pharm Pharmacol 1999, 51:971-974.
• [6]De La Puerta R, Gutierrez VR, Hoult JRS: Inhibition of leukocyte 5-lipoxygenase by phenolics from virgin olive oil. Biochem Pharmacol 1999, 57:445-449.
• [7]Medina E, De Castro A, Romero C, Brenes M: Comparison of the concentrations of phenolic compounds in olive oils and other plant oils: correlation with antimicrobial activity. J Agric Food Chem 2006, 54:4954-4961.
• [8]Medina E, Brenes M, Romero C, García A, De Castro A: Main antimicrobial compounds in table olives. J Agric Food Chem 2007, 55:9817-9823.
• [9]Auñon-Calles D, Giordano E, Bohnenberger S, Visioli F: Hydroxytyrosol is not genotoxic in vitro. Pharmacol Res 2013, 74:87-93.
• [10]OECD Guideline for the Testing of Chemicals: mammalian bone marrow chromosome aberration test. http://www.oecd.org/chemicalsafety/risk-assessment/1948450.pdf webcite
• [11]EFSA Scientific Committee: Scientific opinion on genotoxicity testing strategies applicable to food and feed safety assessment. EFSA J 2011, 9(2379):1-68.
• [12]Directive 2010/63/EU of the European parliament of the council of 22 September 2010 on the protection of animals used for scientific purposes . http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2010:276:0033:0079:en:PDF webcite
• [13]Bouayed J, Bohn T: Exogenous antioxidants - double-edged swords in cellular redox state: Health beneficial effects at physiologic doses versus deleterious effects at high doses. Oxid Med Cell Longev 2010, 3:228-237.
• [14]Bai C, Yan X, Takenaka M, Sekiya K, Nagata T: Determination of synthetic hydroxytyrosol in rat plasma by GC-MS. J Agric Food Chem 1998, 46:3998-4001.
• [15]Manna C, Galletti P, Cucciolla V, Moltedo O, Leone A, Zappia V: The protective effect of the olive oil polyphenol (3,4- dihydroxyphenyl)ethanol counteracts reactive oxygen metabolite-induced cytotoxicity in Caco-2 cells. J Nutr 1997, 127:286-292.
• [16]Hamden K, Allouche N, Damak M, Carreau S, Elfeki A: Inhibitory action of hydroxytyrosol from glucose-induced insulin deficient and pancreas and liver toxicity in vitro. Curr Trends Biotechnol Pharm 2009, 3:352-361.
• [17]Miro-Casas E, Covas MI, Farre M, Fito M, Ortuño J, Weinbrenner T, Roset P, De La Torre R: Hydroxytyrosol disposition in humans. Clin Chem 2003, 49:945-952.
• [18]Tuck KL, Freeman MP, Hayball PJ, Stretch GL, Stupans I: The in vivo fate of hydroxytyrosol and tyrosol, antioxidant phenolic constituents of olive oil, after intravenous and oral dosing of labeled compounds to rats. J Nutr 2001, 131:1993-1996.
• [19]D'Angelo S, Manna C, Migliardi V, Mazzoni O, Morrica P, Capasso G, Pontoni G, Galletti P, Zappia V: Pharmacokinetics and metabolism of hydroxytyrosol, a natural antioxidant from olive oil. Drug Metab Dispos 2001, 29:1492-1498.