רדיקלים חופשיים גורמים לסרטן וגם מרפאים סרטן

אולי נשמע מוזר, אבל זו המציאות. רדיקלים חופשיים הגורמים להרס התא הסרטני נוצרים בטיפולי רדיותרפיה, כימותרפיה ואפילו היפרתרמיה. רדיקלים חופשיים חיוניים גם בהרג חיידקים. אז לא הכל רע ברדיקלים חופשיים. שימוש גורף באנטיאוקסידנטים יכול גם להזיק! Semin Radiat Oncol. 2004 Jul;14(3):259-66. Oxidative stress, redox, AND the tumor microenvironment. Cellular metabolism is critical for the generation of energy in biological systems; however, as a result of electron transfer reactions, reactive oxygen species (ROS) are generated in aerobic cells. Although low amounts of ROS are easily tolerated by the cell, abnormally high levels of ROS induce oxidative stress. ROS are also produced after exposure to ionizing radiation, selected chemotherapeutic agents, hyperthermia, inhibition of antioxidant enzymes, OR depletion of cellular reductants such as NADPH AND glutathione. Oxidative stress such as ionizing radiation produces a variety of highly reactive free radicals that damage cells, initiate signal transduction pathways, AND alter gene expression. Cells are capable of countering the effects of oxidative stress by virtue of a complex redox buffering system. With respect to the radiation treatment of cancer, components of the cellular redox armamentarium may be targeted to enhance cell killing in the case of tumors and/or protection in the case of normal tissues. --------------------------------------------------------- 1: Chem Biol Interact. 2006 Mar 10;160(1):1-40. Free radicals, metals AND antioxidants in oxidative stress-induced cancer. Oxygen-free radicals, more generally known as reactive oxygen species (ROS) along with reactive nitrogen species (RNS) are well recognised for playing a dual role as both deleterious AND beneficial species. The "two-faced" character of ROS is substantiated by growing body of evidence that ROS within cells act as secondary messengers in intracellular signalling cascades, which induce AND maintain the oncogenic phenotype of cancer cells, however, ROS can also induce cellular senescence AND apoptosis AND can therefore function as anti-tumourigenic species. The cumulative production of ROS/RNS through either endogenous OR exogenous insults is termed oxidative stress AND is common for many types of cancer cell that are linked with altered redox regulation of cellular signalling pathways. Oxidative stress induces a cellular redox imbalance which has been found to be present in various cancer cells compared with normal cells; the redox imbalance thus may be related to oncogenic stimulation. DNA mutation is a critical step in carcinogenesis AND elevated levels of oxidative DNA lesions (8-OH-G) have been noted in various tumours, strongly implicating such damage in the etiology of cancer. It appears that the DNA damage is predominantly linked with the initiation process. This review examines the evidence for involvement of the oxidative stress in the carcinogenesis process. Attention is focused on structural, chemical AND biochemical aspects of free radicals, the endogenous AND exogenous sources of their generation, the metal (iron, copper, chromium, cobalt, vanadium, cadmium, arsenic, nickel)-mediated formation of free radicals (e.g. Fenton chemistry), the DNA damage (both mitochondrial AND nuclear), the damage to lipids AND proteins by free radicals, the phenomenon of oxidative stress, cancer AND the redox environment of a cell, the mechanisms of carcinogenesis AND the role of signalling cascades by ROS; in particular, ROS activation of AP-1 (activator protein) AND NF-kappaB (nuclear factor kappa B) signal transduction pathways, which in turn lead to the transcription of genes involved in cell growth regulatory pathways. The role of enzymatic (superoxide dismutase (Cu, Zn-SOD, Mn-SOD), catalase, glutathione peroxidase) AND non-enzymatic antioxidants (Vitamin C, Vitamin E, carotenoids, thiol antioxidants (glutathione, thioredoxin AND lipoic acid), flavonoids, selenium AND others) in the process of carcinogenesis as well as the antioxidant interactions. -------------------------------------------------- Front Biosci. 2006 Jan 1;11:300-12. Oxidative stress AND apoptosis: a new treatment paradigm in cancer. Redox regulation has been shown to be an important component of malignant cell survival. Tipping the cellular redox balance through pharmacologic regulation in favor of increasing intracellular reactive oxygen species (ROS) and/or depleting protective reducing metabolites (such as glutathione AND nicotinamide adenine dinucleotide phosphate) may lead to oxidative stress AND resultant induction of apoptosis for the treatment of cancer. We review the biology AND importance of ROS with regard to malignant AND normal cells. Moreover, we discuss pre-clinical AND clinical data regarding novel therapeutic agents that modulate the cellular redox system including buthionine sulfoximine, ascorbic acid, arsenic trioxide, imexon, AND motexafin gadolinium as single-agents AND in combination. Continued research is needed to better understand the mechanisms AND specific apoptotic pathways involved in ROS-induced cell death, as well as, to determine the most rationale AND effective combination of redox-active agents

J Am Coll Nutr. 2001 Oct;20(5 Suppl):464S-472S The benefits AND hazards of antioxidants: controlling apoptosis AND other protective mechanisms in cancer patients AND the human population. Cellular oxidants, called reactive oxygen species (ROS), are constantly produced in animal AND human cells. Excessive ROS can induce oxidative damage in cell constituents AND promote a number of degenerative diseases AND aging. Cellular antioxidants protect against the damaging effects of ROS. However, in moderate concentrations, ROS are necessary for a number of protective reactions. Thus, ROS are essential mediators of antimicrobial phagocytosis, detoxification reactions carried out by the cytochrome P-450 complex, AND apoptosis which eliminates cancerous AND other life-threatening cells. Excessive antioxidants could dangerously interfere with these protective functions, while temporary depletion of antioxidants can enhance anti-cancer effects of apoptosis. Experimental data are presented supporting these notions. The human population is heterogeneous regarding ROS levels. Intake of exogenous antioxidants (vitamins E, C, beta-carotene AND others) could protect against cancer AND other degenerative diseases in people with innate OR acquired high levels of ROS. However, abundant antioxidants might suppress these protective functions, particularly in people with a low innate baseline level of ROS. Screening human populations for ROS levels could help identify groups with a high level of ROS that are at a risk of developing cancer AND other degenerative diseases. It also could identify groups with a low level of ROS that are at a risk of down-regulating ROS-dependent anti-cancer AND other protective reactions. Screening populations could provide a scientifically grounded application of antioxidant supplements, which could significantly contribute to the nation's health. --------------------------------------------------------- Cancer Res. 2003 Aug 1;63(15):4295-8. The antioxidant conundrum in cancer. The health-related effects of interactions between reactive oxygen species (ROS) AND dietary antioxidants AND the consequences of dietary antioxidant supplementation on human health are by no means clear. Although ROS, normal byproducts of aerobic metabolism, are essential for various defense mechanisms in most cells, they can also cause oxidative damage to DNA, proteins, AND lipids, resulting in enhanced disease risk. Dietary antioxidants (e.g., vitamin E, vitamin C, beta-carotene, AND selenium), as well as endogenous antioxidant mechanisms, can help maintain an appropriate balance between the desirable AND undesirable cellular effects of ROS. However, any health-related effects of interactions between dietary antioxidants AND ROS likely depend on the health status of an individual AND may also be influenced by genetic susceptibilities. Clinical studies of antioxidant supplementation AND changes in either oxidative status, disease risk, OR disease outcome have been carried out in healthy individuals, populations at risk for certain diseases, AND patients undergoing disease therapy. The use of antioxidants during cancer therapy is currently a topic of heated debate because of an overall lack of clear research findings. Some data suggest antioxidants can ameliorate toxic side effects of therapy without affecting treatment efficacy, whereas other data suggest antioxidants interfere with radiotherapy OR chemotherapy. Overall, examination of the evidence related to potential interactions between ROS AND dietary antioxidants AND effects on human health indicates that consuming dietary antioxidant supplements has pros AND cons for any population AND raises numerous questions, issues, AND challenges that make this topic a fertile field for future research. Overall, current knowledge makes it premature to generalize AND make specific recommendations about antioxidant usage for those at high risk for cancer OR undergoing treatment. ------------------------------------------------- CA Cancer J Clin. 2005 Sep-Oct;55(5):319-21. Use of antioxidants during chemotherapy AND radiotherapy should be avoided. • . Many patients being treated for cancer use dietary supplements, particularly antioxidants, in the hope of reducing the toxicity of chemotherapy AND radiotherapy. Some researchers have claimed, furthermore, that antioxidants also increase the effectiveness of cytotoxic therapy AND have explicitly recommended their use. However, mechanistic considerations suggest that antioxidants might reduce the effects of conventional cytotoxic therapies. Preclinical data are currently inconclusive AND a limited number of clinical studies have not found any benefit. Clinicians should advise their patients against the use of antioxidant dietary supplements during chemotherapy OR radiotherapy. Such caution should be seen as the standard approach for any unproven agent that may be harmful.

ידוע שרדיקל חופשי הינו מולקולה או מבנה אטומי חסר אלקטרון המייצג חוסר יציבות ושואף לקבל את האלקטרון החסר. אך האם נכון הדבר שלנוגד חימצון יש בעצם עודף של אלקטרון שבגינו יוכל לנדב וע"י לייצב תאת הריאקציה ??? וכשסוברים שיש נוגדי חימצון חזקים מה המשמעות האמיתי לכך (כגון זרעי ענבים,פיקנוגנול וכיו"ב) ושאלה אחרונה --האם שייך בימינו לטעון שיכולה להיות תגובה לא מבריאה מצריכת יתר של אנטיאוקסידנטים ? ואם כן אנא הסבר מדוע תודה