Dietary oxidative stress and plant extracts tion of reactive species does not necessarily lead to oxidative stress. Similarly, the increased activity of antiox- idant enzymes or the enhanced uptake of antioxidant molecules as dietary components or as nutritional supple- ments is not synonymous with an improved defense against the harmful effects of reactive species. The oxidative agents and the antioxidant mechanisms are in a potential balance, which is disturbed in favor of the former when oxidative stress occurs (Sies 1991). Moreover, although it sounds contradictory, it is an undoubted fact that antioxidants under specific conditions can have a prooxidant action. Over the last two decades, there has been increasing scientific evidence of the beneficial health implications of the Mediterranean diet. Polyphenolic compounds and especially flavonoids are present in its main constituents such as grapes, legumes, other kinds of vegetables, fruits, oil, and wine. Polyphenolic compounds are largely known for their antioxidant properties, but they may also act to favor oxidative stress. This is mainly observed when antioxidant molecules are administered individually and not as a part of the diet. Thus, “a protective effect of diet is not equivalent to a protective effect of antioxidants in diet” (Halliwell 2000). There are studies demonstrating such discrepancies. A diet rich in vegetables and fruits appears to decrease the risk of cancer and to increase the concentration of β-carotene in the blood. On the other hand, administra- tion of β-carotene does not decrease the likelihood of cancer, but has rather the opposite effect in smokers (Rowe 1996). Fruits and vegetables decrease the free radical- induced DNA damage in humans, a risk factor for cancer development. In contrast, ascorbate, vitamin E, or β- carotene administration did not have the same effects in studies reviewed by Halliwell (2000). The phenolic radical, which is formed after scavenging reactive species, may oxidize GSH, generating a thiyl radical (RS⋅) which, reacting with GSH, produces the disulfide radical (GSSG⋅). The latter reduces O2, thus producing Ο2⋅− (Cotelle 2001). Furthermore, the phenolic radical reduces ferric anion (Fe+++) to ferrous anion (Fe++), which can generate the highly reactive OH⋅ by Fenton reaction (Halliwell and Gutteridge 2007). This fact might seem surprising, but it has a reasonable explanation. Reactive species are oxidizing agents and the antioxidants that scavenge them are reducing agents. An antioxidant can be a better scavenger in vitro provided that it has an increased reducing capacity and is administered at a high concentration. Thus, when a single antioxidant molecule is administered alone, its concentration in the blood is higher than when it is taken as an ingredient of vegetables or fruits. Apart from the concentration of an antioxidant, the time of administration is of high impor- tance. Transition metals are generated from metalloproteins as an outcome of oxidative damage and are catalysts of 15 oxidative damage. Thus, administration of potent antiox- idants after oxidative damage might promote further damage, implying potent prooxidant action. A relative study by Kang et al. (1998) observed that the administration of vitamin C was protective against oxidative damage induced by the herbicide paraquat in animals. Nevertheless, when vitamin C was given after animals were exposed to paraquat, it impaired the damage by interacting with the released transition metals (Kang et al. 1998). Although this paradox seems to raise skepticism against the use of antioxidants, it may offer new guidelines in antioxidant administration. Specifically, antioxidants may become more effective and less harmful when administered at the appropriate time points and at the appropriate concentra- tions. This fact could be helpful for athletes who need to enhance their performance or for patients suffering from reactive species-related diseases as an alternative way to improve their health. Exercise, a commonly used oxidant stimulus In the previous sections, the roles of reactive species in several physiological processes were analyzed and the detrimental effects of reactive species and oxidative stress on macromolecules were described. This section will focus on exercise, a very important and commonly examined stimulus of oxidative stress. Exercise is a modality usually adopted as a physiological model for examining the effects of reactive species in human or animal physiology. It demonstrates that reactive species do not always have adverse effects, but they are necessary in physiological processes that are beneficial for human health. A characteristic example of this fact is that the benefits of regular exercise on health are accompanied by repeated episodes of oxidative stress (Fisher-Wellman and Bloomer 2009). Exercise has been previously shown to affect the blood’s redox status and to induce biochemical changes (Nikolaidis and Jamurtas 2009) such as an increase in blood pressure (Nybo et al. 2002), an increase in lactate concentration (Stringer et al. 1994), a decrease in blood pH (Hermansen and Osnes 1972), and a decrease in oxygen partial pressure (Stringer et al. 1994). Specifically, it has been shown that when blood pressure increases, the generation of reactive species in the splachnic circulation of rats increases as well (Hall et al. 1994). Furthermore, lactate seems to be a free radical scavenger and prevents lipid peroxidation by neutralizing OH⋅ and O2⋅−, but not lipid radicals in vitro (Groussard et al. 2000). It has also been proposed that reactive species production in the rat brain mitochondrial respiratory chain is increased in a pH-dependent manner (Selivanov et al. 2008).