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      Investigation on the Protective Effects of Cranberry Against the DNA Damage Induced by Benzo[a]pyrene

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          Abstract

          There are few reports that demonstrate the antigenotoxic potential of cranberries. Although the types of berry fruits consumed worldwide are many, this paper focuses on cranberries that are commonly consumed in Mexico ( Vaccinium macrocarpon species). The purpose of the present study is to determine whether cranberry ethanolic extract (CEE) can prevent the DNA damage produced by benzo[a]pyrene (B[a]P) using an in vivo mouse peripheral blood micronucleus assay. The experimental groups were organized as follows: a negative control group (without treatment), a positive group treated with B[a]P (200 mg/kg), a group administered with 800 mg/kg of CEE, and three groups treated with B[a]P and CEE (200, 400, and 800 mg/kg) respectively. The CEE and benzo[a]pyrene were administered orally for a week, on a daily basis. During this period the body weight, the feed intake, and the determination of antigenotoxic potential were quantified. At the end of this period, we continued with the same determinations for one week more (recovery period) but anymore administration of the substances. The animals treated with B[a]P showed a weight increase after the first week of administration. The same phenomenon was observed in the lots combined with B[a]P and CEE (low and medium doses). The dose of 800 mg/kg of CEE showed similar values to the control group at the end of the treatment period. In the second part of the assay, when the substances were not administered, these experimental groups regained their normal weight. The dose of CEE (800 mg/kg) was not genotoxic nor cytotoxic. On the contrary, the B[a]P increases the frequency of micronucleated normochromatic erythrocytes (MNNE) and reduces the rate of polychromatic erythrocytes (PE) at the end of the treatment period. With respect to the combined lots, a significant decrease in the MN rate was observed from the sixth to the eighth day of treatment with the two high doses applied; the highest protection (60%) was obtained with 800 mg/kg of CEE. The same dose showed an anticytotoxic effect which corresponded to an improvement of 62.5% in relation to the animals administered with the B[a]P. In the second period, all groups reached values that have been seen in the control group animals. Our results suggest that the inhibition of clastogenicity of the cranberry ethanolic extract against B[a]P is related to the antioxidant capacity of the combination of phytochemicals present in its chemical composition.

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          A new approach to practical acute toxicity testing.

          A method for the investigation of the acute toxicity of an unknown chemical substance, with an estimation on the LD50, is described. Using this, it is possible to obtain with 13 experimental animals adequate information on the acute toxicity and on the LD50. This method has no limitations and applies to drugs, agricultural and industrial chemicals. It can be used for every route of administration.
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            Berry phenolics and their antioxidant activity.

            Phenolic profiles of a total of 26 berry samples, together with 2 apple samples, were analyzed without hydrolysis of glycosides with HPLC. The phenolic contents among different berry genera varied considerably. Anthocyanins were the main phenolic constituents in bilberry, bog-whortleberry, and cranberry, but in cowberries, belonging also to the family Ericaceae genus Vaccinium, flavanols and procyanidins predominated. In the family Rosaceae genus Rubus (cloudberry and red raspberry), the main phenolics found were ellagitannins, and in genus Fragaria (strawberry), ellagitannins were the second largest group after anthocyanins. However, phenolic acids were dominant in rowanberries (genus Sorbus) and anthocyanins in chokeberry (genus Aronia). In the family Grossulariaceae genus Ribes (currants and gooseberry), anthocyanins predominated, as well as in crowberries (family Empetraceae genus Empetrum). In apples, hydroxycinnamic acids were the main phenolic subgroup. Extraction methods for berries and apples were studied to produce phenolic extracts with high antioxidant activity. Evaluation of antioxidant activity was performed by autoxidazing methyl linoleate (40 degrees C, in the dark). The extraction method affected remarkably both the phenolic composition and the antioxidant activity, but with statistical analysis the observed activity could not be well explained with the contents of individual phenolic subgroups.
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              A-Type proanthocyanidin trimers from cranberry that inhibit adherence of uropathogenic P-fimbriated Escherichia coli.

              Three proanthocyanidin trimers possessing A-type interflavanoid linkages, epicatechin-(4beta-->6)-epicatechin-(4beta-->8, 2beta-->O-->7)-epicatechin (4), epicatechin-(4beta-->8, 2beta-->O-->7)-epicatechin-(4beta-->8)-epicatechin (5), and epicatechin-(4beta-->8)-epicatechin-(4beta-->8, 2beta-->O-->7)-epicatechin (6), were isolated from the ripe fruits of Vaccinium macrocarpon (cranberry) and prevented adherence of P-fimbriated Escherichia coli isolates from the urinary tract to cellular surfaces containing alpha-Gal(1-->4)beta-Gal receptor sequences similar to those on uroepithelial cells. The structure of 4 was elucidated by a combination of spectroscopic methods and acid-catalyzed degradation with phloroglucinol. Also isolated were the weakly active epicatechin-(4beta-->8, 2beta-->O-->7)-epicatechin (procyanidin A2) (3) and the inactive monomer epicatechin (1) and the inactive dimer epicatechin-(4beta-->8)-epicatechin (procyanidin B2) (2).
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                Author and article information

                Journal
                Molecules
                Molecules
                molecules
                Molecules
                MDPI
                1420-3049
                12 April 2012
                April 2012
                : 17
                : 4
                : 4435-4451
                Affiliations
                [1 ]Institute of Health Sciences, Autonomous University of Hidalgo State, Ex-Hacienda de la Concepción. Pachuca, Hidalgo, 42080, Mexico; Email: cachito_sony@ 123456yahoo.com.mx (S.F.-A.); m.valadezvega@ 123456lycos.com (C.V.-V.); glorias_4020@ 123456yahoo.com.mx (G.S.-S.); zupecl@ 123456yahoo.com.mx (C.Z.P.); spmtz68@ 123456yahoo.com.mx (M.S.-G.); jizquierdovega@ 123456gmail.com (J.A.I.-V.); jmorales101@ 123456yahoo.com.mx (J.A.M.-G.)
                [2 ]Laboratory of Biochemistry and Experimental Medicine, Division of Biomedical Research, National Medical Center “20 de Noviembre”, ISSSTE. México D.F., 03229, Mexico;Email: quauhtlicutli@ 123456yahoo.com
                [3 ]Faculty of Dentistry, School Circuit S/N. UNAM. México D.F., 04510, Mexico; Email: jaime_esquivel2003@ 123456hotmail.com (J.E.-S.); cesquivelch@ 123456gmail.com (C.E.-C.)
                [4 ]Secretary of Research and Graduate Studies, Autonomous University of Nayarit, “City of the culture Amado Nervo”, Boulevard Tepic-Xalisco S/N. Tepic, Nayarit, 28000, Mexico; Email: teresumaya@ 123456hotmail.com
                [5 ]National School of Biological Sciences, IPN. Av. Wilfrido Massieu. Unidad A. López Mateos. Zacatenco. México D.F., 07700, Mexico; Email: fisiobiologo@ 123456hotmail.com (T.F.-A.); jorgemendozaperez@ 123456yahoo.com (J.M.-P.)
                Author notes
                [* ] Author to whom correspondence should be addressedeomsmx@yahoo.com.mx ; Email: eomsmx@ 123456yahoo.com.mx ; Tel./Fax: +52-771-717-2000 (ext. 5113).
                Article
                molecules-17-04435
                10.3390/molecules17044435
                6268607
                22499190
                c225b3b5-61e0-45fc-964e-bccd66661839
                © 2012 by the authors; licensee MDPI, Basel, Switzerland.

                This article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/3.0/).

                History
                : 27 February 2012
                : 19 March 2012
                : 20 March 2012
                Categories
                Article

                cranberries,benzo[a]pyrene,micronucleus assay,antigenotoxic effect

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