Borut Poljšak

Achieving the Balance between ROS and Antioxidants: When to Use the Synthetic Antioxidants

Free radical damage is linked to formation of many degenerative diseases, including cancer, cardiovascular disease, cataracts, and aging. Excessive reactive oxygen species (ROS) formation can induce oxidative stress, leading to cell damage that can culminate in cell death. Therefore, cells have antioxidant networks to scavenge excessively produced ROS. The balance between the production and scavenging of ROS leads to homeostasis in general; however, the balance is somehow shifted towards the formation of free radicals, which results in accumulated cell damage in time. Antioxidants can attenuate the damaging effects of ROS in vitro and delay many events that contribute to cellular aging. The use of multivitamin/mineral supplements (MVMs) has grown rapidly over the past decades. Some recent studies demonstrated no effect of antioxidant therapy; sometimes the intake of antioxidants even increased mortality. Oxidative stress is damaging and beneficial for the organism, as some ROS are signaling molecules in cellular signaling pathways. Lowering the levels of oxidative stress by antioxidant supplements is not beneficial in such cases. The balance between ROS and antioxidants is optimal, as both extremes, oxidative and antioxidative stress, are damaging. Therefore, there is a need for accurate determination of individuals oxidative stress levels before prescribing the supplement antioxidants.

Free Radicals and Extrinsic Skin Aging

Human skin is constantly directly exposed to the air, solar radiation, environmental pollutants, or other mechanical and chemical insults, which are capable of inducing the generation of free radicals as well as reactive oxygen species (ROS) of our own metabolism. Extrinsic skin damage develops due to several factors: ionizing radiation, severe physical and psychological stress, alcohol intake, poor nutrition, overeating, environmental pollution, and exposure to UV radiation (UVR). It is estimated that among all these environmental factors, UVR contributes up to 80%. UV-induced generation of ROS in the skin develops oxidative stress, when their formation exceeds the antioxidant defence ability of the target cell. The primary mechanism by which UVR initiates molecular responses in human skin is via photochemical generation of ROS mainly formation of superoxide anion (O2 − ∙), hydrogen peroxide (H2O2), hydroxyl radical (OH∙), and singlet oxygen (1O2). The only protection of our skin is in its endogenous protection (melanin and enzymatic antioxidants) and antioxidants we consume from the food (vitamin A, C, E, etc.). The most important strategy to reduce the risk of sun UVR damage is to avoid the sun exposure and the use of sunscreens. The next step is the use of exogenous antioxidants orally or by topical application and interventions in preventing oxidative stress and in enhanced DNA repair.

Strategies for Reducing or Preventing the Generation of Oxidative Stress

The reduction of oxidative stress could be achieved in three levels: by lowering exposure to environmental pollutants with oxidizing properties, by increasing levels of endogenous and exogenous antioxidants, or by lowering the generation of oxidative stress by stabilizing mitochondrial energy production and efficiency. Endogenous oxidative stress could be influenced in two ways: by prevention of ROS formation or by quenching of ROS with antioxidants. However, the results of epidemiological studies where people were treated with synthetic antioxidants are inconclusive and contradictory. Recent evidence suggests that antioxidant supplements (although highly recommended by the pharmaceutical industry and taken by many individuals) do not offer sufficient protection against oxidative stress, oxidative damage or increase the lifespan. The key to the future success of decreasing oxidative-stress-induced damage should thus be the suppression of oxidative damage without disrupting the wellintegrated antioxidant defense network. Approach to neutralize free radicals with antioxidants should be changed into prevention of free radical formation. Thus, this paper addresses oxidative stress and strategies to reduce it with the focus on nutritional and psychosocial interventions of oxidative stress prevention, that is, methods to stabilize mitochondria structure and energy efficiency, or approaches which would increase endogenous antioxidative protection and repair systems.

The Role of Antioxidants in Skin Cancer Prevention and Treatment

Skin cells are constantly exposed to reactive oxygen species (ROS) and oxidative stress from exogenous and endogenous sources. UV radiation is the most important environmental factor in the development of skin cancer and skin aging. The primary products caused by UV exposure are generally direct DNA oxidation or generation of free radicals which form and decompose extremely quickly but can produce effects that can last for hours, days, or even years. UV-induced generation of ROS in the skin develops oxidative stress when their formation exceeds the antioxidant defense ability. The reduction of oxidative stress can be achieved on two levels: by lowering exposure to UVR and/or by increasing levels of antioxidant defense in order to scavenge ROS. The only endogenous protection of our skin is melanin and enzymatic antioxidants. Melanin, the pigment deposited by melanocytes, is the first line of defense against DNA damage at the surface of the skin, but it cannot totally prevent skin damage. A second category of defense is repair processes, which remove the damaged biomolecules before they can accumulate and before their presence results in altered cell metabolism. Additional UV protection includes avoidance of sun exposure, usage of sunscreens, protective clothes, and antioxidant supplements.

Skin Photoaging and the Role of Antioxidants in Its Prevention

Photoaging of the skin depends primarily on the degree of ultraviolet radiation (UVR) and on an amount of melanin in the skin (skin phototype). In addition to direct or indirect DNA damage, UVR activates cell surface receptors of keratinocytes and fibroblasts in the skin, which leads to a breakdown of collagen in the extracellular matrix and a shutdown of new collagen synthesis. It is hypothesized that dermal collagen breakdown is followed by imperfect repair that yields a deficit in the structural integrity of the skin, formation of a solar scar, and ultimately clinically visible skin atrophy and wrinkles. Many studies confirmed that acute exposure of human skin to UVR leads to oxidation of cellular biomolecules that could be prevented by prior antioxidant treatment and to depletion of endogenous antioxidants. Skin has a network of all major endogenous enzymatic and nonenzymatic protective antioxidants, but their role in protecting cells against oxidative damage generated by UV radiation has not been elucidated. It seems that skins antioxidative defence is also influenced by vitamins and nutritive factors and that combination of different antioxidants simultaneously provides synergistic effect.

The neglected significance of "antioxidative stress".

Oxidative stress arises when there is a marked imbalance between the production and removal of reactive oxygen species (ROS) in favor of the prooxidant balance, leading to potential oxidative damage. ROSs were considered traditionally to be only a toxic byproduct of aerobic metabolism. However, recently, it has become apparent that ROS might control many different physiological processes such as induction of stress response, pathogen defense, and systemic signaling. Thus, the imbalance of the increased antioxidant potential, the so-called antioxidative stress, should be as dangerous as well. Here, we synthesize increasing evidence on “antioxidative stress-induced” beneficial versus harmful roles on health, disease, and aging processes. Oxidative stress is not necessarily an un-wanted situation, since its consequences may be beneficial for many physiological reactions in cells. On the other hand, there are potentially harmful effects of “antioxidative stress,” especially in the cases of overconsumption of synthetic antioxidants. Antioxidants can neutralize ROS and decrease oxidative stress; however, this is not always beneficial in regard to disease formation or progression (of, e.g., cancer) or for delaying aging.

Interference of chromium with biological systems in yeasts and fungi: A review

This paper deals with the interactions of chromium (Cr) with biological systems, focusing in particular on yeasts and fungi. These interactions are analysed with primarily regard to biochemical functions, but higher levels of organization are also considered. Thus, the morphological and cytological characteristics of selected microorganisms in response to exposure to chromium ions are evaluated. The different oxidation states of chromium and reactive oxygen species (ROS) generated in redox reactions with chromium ions are presented and characterized. The interactions of the most exposed subcellular structures, including the cell wall, plasma membrane and nuclei, have been deeply investigated in recent years, for two major reasons. The first is the toxicity of chromium ions and their strong impact on the metabolism of many species, ranging from microbes to humans. The second is the still disputed usefulness of chromium ions, and in particular trivalent chromium, in the glucose and fat metabolisms. Chromium pollution is still an important issue in many regions of the world, and various solutions have been proposed for the bioremediation of soil and water with selected microbial species. Yeasts and especially moulds have been most widely investigated from this aspect, and the biosorption and bioaccumulation of chromium for bioremediation purposes have been demonstrated. Accordingly, the mechanisms of chromium tolerance or resistance of selected microbes are of particular importance in both bioremediation and waste water treatment technologies. The mechanisms of chromium toxicity and detoxification have been studied extensively in yeasts and fungi, and some promising results have emerged in this area. (© 2010 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)

Adaptive response, evidence of cross-resistance and its potential clinical use.

Organisms and their cells are constantly exposed to environmental fluctuations. Among them are stressors, which can induce macromolecular damage that exceeds a set threshold, independent of the underlying cause. Stress responses are mechanisms used by organisms to adapt to and overcome stress stimuli. Different stressors or different intensities of stress trigger different cellular responses, namely induce cell repair mechanisms, induce cell responses that result in temporary adaptation to some stressors, induce autophagy or trigger cell death. Studies have reported life-prolonging effects of a wide variety of so-called stressors, such as oxidants, heat shock, some phytochemicals, ischemia, exercise and dietary energy restriction, hypergravity, etc. These stress responses, which result in enhanced defense and repair and even cross-resistance against multiple stressors, may have clinical use and will be discussed, while the emphasis will be on the effects/cross-effects of oxidants.

The Protective Role of Antioxidants in the Defence against ROS/RNS-Mediated Environmental Pollution

Overproduction of reactive oxygen and nitrogen species can result from exposure to environmental pollutants, such as ionising and nonionising radiation, ultraviolet radiation, elevated concentrations of ozone, nitrogen oxides, sulphur dioxide, cigarette smoke, asbestos, particulate matter, pesticides, dioxins and furans, polycyclic aromatic hydrocarbons, and many other compounds present in the environment. It appears that increased oxidative/nitrosative stress is often neglected mechanism by which environmental pollutants affect human health. Oxidation of and oxidative damage to cellular components and biomolecules have been suggested to be involved in the aetiology of several chronic diseases, including cancer, cardiovascular disease, cataracts, age-related macular degeneration, and aging. Several studies have demonstrated that the human body can alleviate oxidative stress using exogenous antioxidants. However, not all dietary antioxidant supplements display protective effects, for example, β-carotene for lung cancer prevention in smokers or tocopherols for photooxidative stress. In this review, we explore the increases in oxidative stress caused by exposure to environmental pollutants and the protective effects of antioxidants.

Prevention of intracellular oxidation in yeast: the role of vitamin E analogue, Trolox (6-hydroxy-2,5,7,8-tetramethylkroman-2-carboxyl acid)

Reactive oxygen species (ROS) are not only generated in conditions of cellular stress but are also constitutively produced in most cell types by specific metabolic processes. This research focused on a potential antioxidant Trolox (model compound for α‐tocopherol), with the aim to establish exact mechanisms of Trolox intracellular oxidation prevention on model organism Saccharomyces cerevisiae. Measuring intracellular oxidation of Trolox‐treated yeast cells revealed that Trolox decreased intracellular oxidation during normal metabolism. Trolox treatment decreased cyto‐ and geno‐toxicity of treated yeast cells in MES buffer, lowered intracellular oxidation, decreased intracellular peroxides formation, and increased H2O2 degradation and superoxide quenching yeast extract ability.