Cell Stress and Chaperones (2012) 17:11–21 DOI 10.1007/s12192-011-0293-3 MINI REVIEW Dietary oxidative stress and antioxidant defense with an emphasis on plant extract administration Aristidis S. Veskoukis & Aristidis M. Tsatsakis & Dimitrios Kouretas Received: 21 July 2011 / Revised: 11 September 2011 / Accepted: 13 September 2011 / Published online: 30 September 2011 # The Author(s) 2011. This article is published with open access at Springerlink.com Abstract Eukaryotic cells generally function in a re- duced state, but an amount of reactive species is essential for several biochemical processes. The antioxidant network is the defensive mechanism that occurs when the concentration of reactive species exceeds a threshold. Polyphenolic compounds present in plant extracts are potent antioxidants in vitro, but they may promote oxidative stress when administered in animals and humans, especially when given as supplements in exercise, a modality usually adopted as an oxidant stimulus. This is mainly observed when antioxidant molecules are administered separately and not as part of a diet. Exercise is usually adopted as a physiological model for examining the effects of reactive species in human or animal physiology. The use of exercise as a model demonstrates that reactive species do not always have adverse effects, but are necessary in physiological processes that are beneficial for human health. This review summarizes what is known about antioxidant supplementation and demonstrates the need for a metic- ulous examination of the in vitro findings before applying them to in vivo models. The term “antioxidant” seems elusive, and it is more appropriate to characterize a compound as “antioxidant” if we know in which A. S. Veskoukis : D. Kouretas Department of Biochemistry and Biotechnology, University of Thessaly, Larissa 41221, Greece A. M. Tsatsakis (*) Forensic Sciences and Toxicology Department, Medical School, University of Crete, 71003 Heraklion, Crete P.O. Box 1393, Greece e-mail: aris@med.uoc.gr concentration it is used, when it is used, and under which conditions. Keywords Antioxidants . Plant extracts . Exercise . In vitro . In vivo . Reactive species Biochemistry of reactive species: an overview Reactive species are unstable, highly reactive structures. They may be free radicals which possess an unpaired electron in their outer orbit and are capable of independent existence. Their half-lives vary from a few nanoseconds for the most reactive compounds to seconds and hours for rather stable radicals. They trigger chain reactions resulting in the oxidation of macromolecules in order to reach a steady state. They are divided into four main categories based on their central atom, specifically reactive oxygen species (ROS), reactive nitrogen species (RNS), reactive sulfur species, and reactive chloride species, derived from oxygen, nitrogen, sulfur, and chloride, respectively (Halliwell and Gutteridge 2007). ROS is the main category of reactive species produced from molecular oxygen (Ο2) with partial chemical reductions. One of the most abundant reactive species is superoxide anion (Ο2⋅−), which is generated by Ο2 following reduction by one electron. When Ο2 is reduced by two and three electrons, hydrogen peroxide (H2O2) and hydroxyl radical (OH⋅) are produced, respectively. Finally, H2O is produced after the full reduction of Ο2 by four electrons (Simic 1988). The most harmful reactive species is OH⋅, which is generated by Fenton and Haber–Weiss reactions in the presence of a transition metal, usually iron (Fe) or copper (Cu). Hydrogen peroxide has a relatively long half-life and can