Review: current topicChronic consumption of a flavanol- and procyanindin-rich diet is associated with reduced levels of 8-hydroxy-2′-deoxyguanosine in rat testes☆
Introduction
There is increasing interest in the identification of dietary factors that can reduce an individual’s risk for chronic disease. In addition to the well-recognized essential nutrients, food can contain a multitude of other components that can promote health. In this regard, flavonoids represent a class of phytochemicals that has been postulated to have positive health effects, and the consumption of certain foods and beverages rich in these compounds has been reported to be associated with numerous positive health benefits including vessel relaxation, reductions in platelet reactivity, and increases in plasma antioxidant potential [1], [2], [3], [4], [5], [6].
Given the chemical diversity of the flavonoid family, it is reasonable to speculate that the biological effects of these compounds in humans occur through a variety of mechanisms. With the above stated, a number of research groups have suggested that an important role for these nutrients can be to enhance the oxidant defense system. Using a variety of in vitro models, investigators have shown that the flavonoids found in wine, purple grape juice, tea, and cocoa can act as potent antioxidants by scavenging reactive radicals, thus reducing the rate of protein and lipid oxidation [7], [8], [9], [10], [11], [12], [13]. While a substantial body of literature has been developed on the antioxidant effects of flavonoids in vitro, studies documenting the potential of flavonoids to reduce oxidative damage in vivo are more limited. The paucity of in vivo data can be attributed, at least in part, to the difficulty in accurately measuring oxidative damage in vivo. For tissue oxidative damage, two markers that are reputed to be reliable indicators of oxidative damage are F2-isoprostanes, [14] a marker of lipid oxidation, and 8-hydroxy-2′-deoxyguanosine (8OH2′dG) [15] a marker of DNA oxidation. In one of the few studies that have demonstrated an in vivo effect of flavonoids on tissue oxidative damage, the consumption of a flavonoid-rich red wine was associated with a reduction in plasma and urinary F2-isoprostanes in smokers [16]. In addition, a few studies have shown that treating rats with flavonoids isolated from black tea and red wine significantly reduced the amount of chemically induced 8OH2′dG adducts in both the colonic mucosa and liver [17], [18], [19].
Cocoa contains a relatively high concentration of flavonoids, specifically the flavanols epicatechin, catechin, and oligomers of epicatechin known as procyanidins [20]. Purified flavonoids isolated from cocoa have been shown to reduce the rate of LDL oxidation in vitro [8], [11], and LDL isolated from the plasma of subjects who consumed flavonoid-rich cocoa has been reported to be more resistant to oxidation ex vivo [12], [21]. The above work supports the concept that diets rich in certain flavonoids may be associated with improvements in the oxidant defense system. In addition, numerous other studies suggest that the consumption of flavonoids may have the potential to prevent oxidative damage in vivo.
The purpose of the current study, using a rodent model, was to determine if the addition of a flavonoid-rich cocoa to a typical control diet would result in a reduction in markers of oxidative damage in animals fed the diet for two weeks in the absence of an oxidative stress.
Section snippets
Materials
All chemicals used were from Sigma (St. Louis, MO) unless otherwise noted. Alkaline phosphatase and nuclease P1 used for enzymatic hydrolysis of DNA were from Roche (Indianapolis, IN). HPLC solvents were from Fisher (Pittsburg, PA). The flavonoid rich cocoa was generously provided by Mars, Incorporated (Hackettstown, NJ).
Animals
The animal protocol was in accordance with NRC recommendations [22] and was approved by the University of California, Davis Animal Use and Care Committee. Forty-eight adult
Results
Food intake and weight gains were similar among the groups (data not shown). As depicted in Fig. 1, plasma epicatechin concentrations increased in a dose-dependent manner according to the concentration of cocoa in the diet. Plasma catechin and dimer in the plasma were below the limit of detection in the plasma of rats in the low cocoa diet groups. Catechin was detected in plasma obtained from rats fed the 2% cocoa diet (40.2 nM ± 1.23) but at a much lower concentration than epicatechin (790.3
Discussion
The results of this work support the concept that the chronic consumption of a diet rich in certain flavonoids can be associated with improvements in the oxidant defense system. Significantly, there was a strong inverse correlation between plasma epicatechin concentrations and testes 8OH2′dG levels. Previous experiments with flavonoids have shown an inverse association between dietary flavonoid intake and tissue oxidative damage when the study subjects were challenged with an oxidative stress
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Characterization of secondary metabolites from green cocoa beans using focusing-modulated comprehensive two-dimensional liquid chromatography coupled to tandem mass spectrometry
2018, Analytica Chimica ActaCitation Excerpt :Moreover, the amount of total oligomeric procyanidins directly affects astringency and bitterness [14], whereas the interaction of these polyphenols with proteins forming complexes affects the cocoa aromatic precursors [15]. Many studies have evaluated the biological properties of PAs suggesting that these polyphenols may confer positive effects including antioxidant activity at different levels [16,17], anti-carcinogenic activity reducing the oxidative DNA damage [18], chemopreventive action [19], positive effects on cardiovascular health [20], and anti-inflammatory and immune-modulatory activities [21]. However, the bioavailability, bioactivity and potential nutraceutical properties largely depend on the composition and concentration of the particular procyanidins found [22].
The effects of cocoa supplementation, caloric restriction, and regular exercise, on oxidative stress markers of brain and memory in the rat model
2013, Food and Chemical ToxicologyCitation Excerpt :Cocoa supplementation did not change ROS concentrations in brain nor the levels of carbonyl, BDNF and memory function. It is possible, we were not able to measure this modification, because the cocoa ingestion dose was inadequate, albeit we used similar amounts as Orozco et al. (2003). However, it must be mentioned that in the study of Orozco et al. (2003), 8-hydroxy-2′-deoxyguanosine, F(2)-isoprostanes, thiobarbituric acid reactive substances and glutathine levels were used as markers of oxidative stress, and actually showed that cocoa supplementation reduced the levels of 8-hydroxy-2′-deoxyguanosine in testes but not in liver and heart.
Chemical Properties, Bioavailability, and Metabolomics of Fruit Proanthocyanidins
2013, Polyphenols in Human Health and DiseaseApple Polyphenols in Cancer Prevention
2013, Polyphenols in Human Health and DiseaseRestoration of arsenite induced hepato-toxicity by crude tannin rich fraction of Theobroma cacao in Sprague Dawley rats
2013, Food Research InternationalDietary flavonoids: Role of (-)-epicatechin and related procyanidins in cell signaling
2011, Free Radical Biology and MedicineCitation Excerpt :In this regard, high concentrations are usually required to act as a direct antioxidant but significantly lower concentrations to act as an indirect antioxidant [31–35]. Many plant polyphenols and flavonoids, including flavanols and procyanidins, are often categorized as in vivo antioxidants because: (i) they have chemical structures that support direct antioxidant reactions affecting both the steady-state concentration (production and metabolism) of cell oxidants and the occurrence of oxidant-mediated events [36,37]; (ii) it has been extensively demonstrated that supplementing the diet of experimental animals and humans with flavonoids reduces the oxidation levels in various organs [38–47]; and (iii) significant evidence shows that certain flavanols and procyanidins can provide benefits in pathological situations associated with high oxidant production, for example, hypertension and cardiovascular disease, and affect markers of oxidative stress [44,46]. However, such direct antioxidant actions in vivo are likely to be significant in tissues exposed to high concentrations of polyphenols, e.g., in the digestive tract where flavanol and procyanidin concentrations can reach values in the upper micromolar range.
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Supported in part by a grant from the National Institutes of Health (DK-35747) and a gift from Mars Incorporated.