Cytogenetic Effects of Grape Extracts (Vitis vinifera) and Polyphenols on Mitomycin C-Induced Sister Chromatid Exchanges (SCEs) in Human Blood Lymphocytes

Abstract

In the present study, the effects of extracts and polyphenol-rich fractions as well as monomer polyphenols identified in them, from both red and white grapes, on mitomycin C (MMC) induced sister chromatid exchanges (SCEs) in human peripheral blood lymphocytes were investigated. The grape extracts and two of the three polyphenol-rich fractions promoted MMC-induced SCEs at concentrations from 75 to 300 microg/mL. However, none of the extracts or fractions alone induced SCEs. Thus, these results suggest caution especially with regard to the use of grape extracts as dietary supplements. On the other hand, the fact that these extracts were not genotoxic alone may indicate a selective activity against genetically damaged cells. This is the first study regarding the clastogenic effects of grape extracts in human cells. Moreover, from the tested polyphenols, caffeic acid, gallic acid, and rutin hydrate enhanced MMC-induced clastogenicity, whereas ferulic acid, protocatechuic acid, (+)-catechin, (-)-epicatechin, and trans-resveratrol had no effect at concentrations between 5 and 100 microM. The differences in the chemical structures of the tested polyphenols may account for their differential effects on MMC clastogenicity.

Safety Assessment of Vitis vinifera (Grape)-Derived Ingredients as Used in Cosmetics

“…No evidence of adverse biological activity 39 Lutein/esters Single-dose, 4-week, and 13-week oral studies found no evidence of toxicity 39 Chlorogenic acid An antioxidant that inhibited tumor promotion by phorbol esters in mice; some controversy exists over allergic reactions in green coffee beans, but it was accepted that chlorogenic acid was not the allergen 39 In mice, 2% (20 000 ppm) chlorogenic acid in the diet for 96 weeks induced papillomas and carcinomas of the forestomach, alveolar type II-cell tumors of the lung, and renal cell adenomas; few toxic effects resulted from acute exposure; subchronic dietary exposures did not induce clinical symptoms of toxicity, however, reduced kidney and adrenal wts and hyperplasia of the forestomach were observed; some genotoxic effects seen in vitro but not in vivo 40 Coumarin Limited evidence in experimental animals for carcinogenicity; not classifiable as to its carcinogenicity in humans (IARC) 41 Flavonoids Epidemiological studies implicated high dietary intake levels of flavonoids in heart disease, but a study of cancer risk failed to find a link; some evidence of genotoxicity in bacterial assays, but a European Organization of Cosmetic Ingredients Industries and Services (UNITIS) report stated that flavonoids do not appear to be genotoxic to mammals in vivo; flavonoids are not considered allergens 39 Quercetin Genotoxic in vitro but not in vivo; some evidence for carcinogenicity (renal tumors) was found in one of the several studies, in 1 species (rat), in 1 gender (male); antioxidant properties noted; estrogenic properties, similar to other flavonoids, were noted; overall conclusion by the Council of Europe Committee of Experts on Cosmetic Products was that quercetin did not present potential risks for human health, but that skin effects and dermal penetration data were needed to complete a toxicological profile; a weight of evidence approach supported a finding that at estimated dietary levels of as a dietary supplement (200-1200 mg/d), adverse health effects would not be produced; reduced histamine release from antigen-induced human basophil cells 39 Quercetin alone, 100 mmol/L, increased the spontaneous number of SCEs in human lymphocytes; however, 50 and 100 mmol/L inhibited mitomycin C (MMC)-induced SCEs in a dose-dependent manner 31 (þ)-Catechin; (-)-epicatechin…”

“…30 It has also been shown that the amount of a constituent present in an extract is dependent on the medium used during extraction and the variety of vitis vinifera (grape) used. 31 For example, a red grape methanolic extract, red grape water extract, white grape methanolic extract, and white grape water extract each contained 0.22, 0.04, 0.01, and 0.02 mg/g transresveratrol, respectively; 0.9, 0.35, 2.25, and 4.09 mg/g (þ)-catechin, respectively; 1.1, 0.32, 1.08, and 2.10 mg/g (-)-epicatechin, respectively; and 0, 0.13, 0.04, and 0.03 mg/g quercetin, respectively.…”

Επίδραση Της Χορήγησης Αλοπουρινόλης Στο Οξειδωτικό Στρες Κατά Την Άσκηση

“…Το είδος σταφυλιών Vitis vinifera καλλιεργείται στην Ελλάδα και βρέθηκε ότι τα εκχυλίσματα από τα σταφύλια του είδους αυτού έχουν αντιοξειδωτικές και χημειοπροστατευτικές ιδιότητες (Stagos et al, 2004(Stagos et al, , 2005(Stagos et al, , 2007. Οι βιολογικές ιδιότητες των σταφυλιών αποδίδονται εν μέρει στις αντιοξειδωτικές ιδιότητες διάφορων συστατικών τους, όπως τα φαινολικά οξέα, οι φλαβανόλες, οι φλαβονόλες, οι ανθοκυανίνες και τα στιλβένια (Renaud & de Lorgeril, 1992;Revilla & Ryan, 2000;.…”

“…Πιο συγκεκριμένα, τα εκχυλίσματα της ποικιλίας αυτής και οι πολυφαινόλες που περιέχονται σε αυτά έχουν ισχυρές αντιοξειδωτικές και χημειοπροστατευτικές ιδιότητες και προστατεύουν το DNA από τη δράση των ελευθέρων ριζών (Stagos et al, 2005). Επιπλέον, έδειξαν αντιμεταλλαξιγόνες ιδιότητες ενάντια στην προκαλούμενη από μπλεομυκίνη μεταλλαξιγένεση στην Salmonella typhimurium TA102 (Stagos et al, 2004) και τις προκαλούμενες από τη μιτομυκίνη c χρωματιδιακές ανταλλαγές σε ανθρώπινα λεμφοκύτταρα (Stagos et al, 2007).…”

“…Έτσι, ο όρος «αντιοξειδωτικό» δεν είναι κάτι απόλυτο αλλά εξαρτάται από τη συγκέντρωση και το σύστημα που μελετάται. Ένα από τα εκχυλίσματα με τις πιο ισχυρές αντιοξειδωτικές ιδιότητες in vitro (Stagos et al, 2005(Stagos et al, , 2007 αλλά και με ανασταλτική δράση στην οξειδάση της ξανθίνης, αυτό από τον καρπό του σταφυλιού της ποικιλίας μπατίκι Τυρνάβου χορηγήθηκε σε επίμυες πριν από την άσκηση. Σκοπός ήταν να ελεγχθεί αν οι in vitro αντιοξειδωτικές του ιδιότητες θα επιβεβαιωθούν in vivo και αν η in vitro ανασταλτική του δράση απέναντι στην οξειδάσης της ξανθίνης θα έχει επίδραση στην απόδοση, όπως η αλοπουρινόλη.…”