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Free Radicals In Biology And Medicine



FRRPB is an interdisciplinary graduate program that provides students with a fundamental grounding in Free Radical Biology and Radiation Biology. All students devise an individualized program to apply the basics of free radical biology to their research program on the fundamental mechanisms and treatment of disease.




Free radicals in biology and medicine



2-Postdoctoral Program in Free Radical and Radiation Biology:FRRBP has a formal, NIH grant supported Training Program for Postdoctoral Scholars. The FRRBP is involved in three major activities related to radiation, free radical, and cancer biology at The University of Iowa; these are:Teaching: involves the organization and presentation of courses within the FRRB Program and other graduate and undergraduate courses, teaching radiation biology to residents in Radiation Oncology and Diagnostic Radiology, to fourth year medical students, and to Nuclear Medicine and X-ray technologists.


Research: in the FRRB Program is investigating the fundamental biology of free radicals and related oxidants and antioxidants in health and disease. This includes, the role of these species in proliferative diseases, such as cancer; antitumor therapy; radiation-induced alterations in gene expression; redox regulation of transcription factor activation, oncogenes and suppressor genes; carcinogenesis; gene therapy; epigenetic effects; pathogenesis of radiation-induced normal tissue injury; cell population kinetics in normal and malignant tissues.


Free Radical Biology and Medicine is a peer-reviewed scientific journal and official journal of the Society for Redox Biology and Medicine. The journal covers research on redox biology, signaling, biological chemistry and medical implications of free radicals, reactive species, oxidants and antioxidants.


The mission of the UAB Center for Free Radical Biology (CFRB) is to create an outstanding research and training environment for elucidating mechanisms and biology of free radicals and redox signaling, and translating these to improve human health and disease.


Free radicals are highly unstable molecules that attempt to achieve a more stable state by reacting with other atoms or molecules in the cell. The four primary types of chemical reactions that free radicals undergo are:


Besides the ROS generation that occurs naturally in the body, humans are constantly exposed to environmental free radicals, including ROS, in the form of radiation, UV light, smog, tobacco smoke, and certain compounds referred to as redox cycling agents, which include some pesticides, but also certain medications used for cancer treatment. The toxicity of these medications against tumor cells (as well as normal body cells) results from the fact that the compounds are modified by cellular enzymes to an unstable intermediate, which then reacts with molecular oxygen to produce the original product plus a superoxide radical. Thus, a vicious cycle of chemical reactions involving these compounds continually produces ROS.


During aging, and in several age-related disease processes, vital cellular proteins, lipids, and DNA and RNA are damaged by free radicals produced by metabolism, chronic inflammation, radiation, smoke, pollution, and many foods and drugs. These oxidized, non-functional, or dysfunctional cellular constituents must be removed or repaired before they cause further cell damage.


When oxygen molecules split into single atoms that have unpaired electrons, they become unstable free radicals that seek other atoms or molecules to bond to. If this continues to happen, it begins a process called oxidative stress.


The free radical theory of aging is relatively new, but numerous studies support it. Studies on rats, for example, showed significant increases in free radicals as the rats aged. These changes matched up with age-related declines in health.


Research on rats suggests that free radicals produced in the mitochondria damage the substances that the cell needs to work properly. This damage causes mutations that produce more free radicals, thus accelerating the process of damage to the cell.


This theory helps explain aging, since aging accelerates over time. The gradual, but increasingly rapid buildup of free radicals offers one explanation for why even healthy bodies age and deteriorate over time.


Antioxidants are chemicals that lessen or prevent the effects of free radicals. They donate an electron to free radicals, thereby reducing their reactivity. What makes antioxidants unique is that they can donate an electron without becoming reactive free radicals themselves.


No single antioxidant can combat the effects of every free radical. Just as free radicals have different effects in different areas of the body, every antioxidant behaves differently due to its chemical properties.


Thousands of chemicals can act as antioxidants. Vitamins C, and E, glutathione, beta-carotene, and plant estrogens called phytoestrogens are among the many antioxidants that may cancel out the effects of free radicals.


It is possible that free radicals are an early sign of cells already fighting disease, or that free radical formation is inevitable with age. Without more data, it is impossible to understand the problem of free radicals fully.


People interested in fighting free radical-related aging should avoid common sources of free radicals, such as pollution and fried food. They should also eat a healthful, balanced diet without worrying about supplementing with antioxidants.


Free radicals, the targets of antioxidants, are a highly reactive species, generated during normal metabolism. Overproduction of free radicals or decreased antioxidant defense due to environmental factors including chemicals, cigarette smoke, ultraviolet radiation and genetic factors, may contribute to development of pathological conditions such as hypertension, metabolic syndrome, diabetic, atherosclerosis, aging, Alzheimer's and Parkinson's, cancer and AIDS.


Most biologically relevant radicals are far too short-lived to be directly detected in biological specimens. For this reason, FRIMCORE employs spin traps and hydroxylamine spin probes as the most definitive and quantitative methods for free radical detection. A newly developed HPLC method allows unequivocal, highly sensitive and quantitative detection of superoxide and peroxynitrite by analysis of specific fluorescent products of dihydroethidium, MitoSOX or boronate probes.


FRIMCORE continues to develop new methods and improves existing protocols for detection of various ROS in biological samples. Our new hydroxylamine spin probes detect free radicals even in strongly scattering media using minimal amounts of biological material while development of new fluorescent probes increases sensitivity and throughput of ROS detection. We closely follow potential artifacts and provide validation of our protocols for the most definitive methods for ROS detection and quantification.


Further work by Fridovich, McCord, and others in the years since revealed a much larger family of molecules that oxygen-breathing plants and animals use to scavenge potentially damaging free oxygen radicals.


Researchers have also studied antioxidants in laboratory experiments. These experiments showed that antioxidants interacted with free radicals and stabilized them, thus preventing the free radicals from causing cell damage.


This hypothesis paper reviews diverse evidence suggesting that intracolonic production of oxygen radicals may play a role in carcinogenesis. The hypothesis began to evolve when the author made the chance discovery that 1/10,000 dilutions of feces generated detectable quantities of highly reactive hydroxyl radicals (HO). The rate of HO formation, detected using DMSO as a molecular probe, was quite remarkable, corresponding to that which would be produced by over 10,000 rads of gamma irradiation per day, absorbed in the periphery of the fecal mass adjacent to the mucosa. The relatively high concentrations of iron in feces, together with the ability of bile pigments to act as iron chelators that support Fenton chemistry, may very well permit efficient HO generation from superoxide and hydrogen peroxide produced by bacterial metabolism. Such free radical generation in feces could provide a missing link in our understanding of the etiology of colon cancer: the oxidation of procarcinogens either by fecal HO, or by secondary peroxyl radicals (ROO) to form active carcinogens or mitogenic tumor promotors. Intracolonic free radical formation may explain the high incidence of cancer in the colon and rectum, compared to other regions of the GI tract, as well as the observed correlations of a higher incidence of colon cancer with red meat in the diet, which increases stool iron, and with excessive fat in the diet, which may increase the fecal content of procarcinogens and bile pigments.


Litterio MC, Jaggers G, Sagdicoglu Celep G, Adamo AM, Costa MA, Oteiza PI, Fraga CG, Galleano M. Blood pressure-lowering effect of dietary (-)-epicatechin administration in L-NAME-treated rats is associated with restored nitric oxide levels. Free radical biology & medicine 2012;53(10):1894-902. [PubMed]


Queisser N, Schupp N, Stopper H, Schinzel R, Oteiza PI. Aldosterone increases kidney tubule cell oxidants through calcium-mediated activation of NADPH oxidase and nitric oxide synthase. Free radical biology & medicine 2011;51(11):1996-2006. [PubMed]


Mackenzie GG, Salvador GA, Romero C, Keen CL, Oteiza PI. A deficit in zinc availability can cause alterations in tubulin thiol redox status in cultured neurons and in the developing fetal rat brain. Free radical biology & medicine 2011;51(2):480-9. [PubMed]


Free radicals are oxygen-containing molecules with an uneven number of electrons. This uneven number of electrons allows free radicals to react easily with other molecules. Free radicals can cause large chain chemical reactions in your body because they react so easily with other molecules. These reactions are called oxidation. They can be beneficial or harmful. 041b061a72


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