Toxicological vs Physiological Functions Of Ros

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During the normal aerobic metabolism, ROS are generated at low levels as unwanted by-products as a consequence of the transfer of a single electron. ROS, which include oxygen free radicals and their nonradical derivatives, play an integral role in maintaining and modulating a wide spectrum of vital physiological functions. In recent years, it has become more apparent that ROS are important mediators of intracellular signaling and redox regulation responsible for cellular home-ostasis (4-6). In fact, some growth factors, cytokines, hormones, and neurotransmitters utilize ROS as secondary messengers in executing normal physiological processes (7). However, excessive production of ROS by exogenous redox chemicals, physical agents (e.g., ultraviolet and ionizing radiations), bacterial or viral infection, or under abnormal pathophysiologic conditions such as oxygen shortage (hypoxia) can be destructive. ROS not only induce direct damage to critical biomolecules, such as DNA, proteins, membrane lipids, and carbohydrates but also indirectly alter or dysregulate the cellular signaling events (Fig. 1). The pathophysiological consequences of such oxidative injury include cancer, neurodegenerative disorders, diabetes, rheumatoid arthritis, etc. Multiple lines of compelling evidence from laboratory and clinical studies support the involvement of ROS as a major cause of cellular injuries in a number of human diseases. ROS hence elicit a wide spectrum of toxico-logic as well as physiologic responses.

Oxidative stress refers to the situation of a serious imbalance or mismatched redox equilibrium between production of ROS and the ability of cells to defend against them. Oxidative

Direct du m age to proteins, lipids, and carbohydrates carbohydrates

Depletion or attenuation of ccllutar antioxidant defense molecules

Genomic DNA (Hase modifications. Slrand breakage, rte)

Cell signal transduction

Oxidative modification of transcriptional activators and protein kinase cascades

DMA Mutations

Dysresulation of Cell Growth, Differentiation and Death

Figure 1 Direct vs. indirect effects of ROS.

stress thus occurs when the production of ROS increases, elimination of ROS or repair of oxidatively damaged macro-molecules decreases, or both. Narrowly interpreted, the family of ROS consists of superoxide radical anion (O2-), hydroperoxyl radical (HO2 ), hydrogen peroxide (H2O2), and hydroxyl radical (HO ). Superoxide, its protonated form HO2', and HO' are relatively short-lived, whereas H2O2 is comparatively stable and can cross cell membranes.

H2O2 is a representative ROS that is produced through auto-oxidation of redox xenobiotics as well as incomplete oxidation in the electron transport chain via dismutation of resultant superoxide by superoxide dismutase (SOD). H2O2 is recently considered to play a pivotal role as a messenger in intracellular signaling cascades (5,8,9). Though not reactive per se, H2O2 forms highly reactive hydroxyl radical by the Fenton reaction in the presence of transition metal ion. Hydroxyl radical reacts rapidly with almost every critical cellular macromolecules including DNA, lipids, and proteins, and thereby causes functional as well as structural alterations in these biomolecules. Enzymatic and nonenzymatic antioxidants detoxify H2O2 and other ROS and minimize damage to critical biomolecules.

Figure 2 Differential effects of ROS.

Typically, low concentrations of ROS are mitogenic, and promote cell proliferation, while intermediate concentrations result in either temporary or permanent growth arrest, such as replicative senescence. Severe oxidative stress ultimately causes cell death via either apoptotic or necrotic mechanisms (Fig. 2).

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Good Carb Diet

Good Carb Diet

WHAT IT IS A three-phase plan that has been likened to the low-carbohydrate Atkins program because during the first two weeks, South Beach eliminates most carbs, including bread, pasta, potatoes, fruit and most dairy products. In PHASE 2, healthy carbs, including most fruits, whole grains and dairy products are gradually reintroduced, but processed carbs such as bagels, cookies, cornflakes, regular pasta and rice cakes remain on the list of foods to avoid or eat rarely.

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