1 / 34

Free Radicals and Antioxidants in Obstetrics and Gynecology

30/08/2002. Antioxidants in Obstetrics and Gynaecology - Prof.S.N.Panda

archibald
Download Presentation

Free Radicals and Antioxidants in Obstetrics and Gynecology

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

    1. Free Radicals and Antioxidants in Obstetrics and Gynecology Prof.Surendra Nath Panda, M.S & Dr.Sasmita Das, M.B.B.S. Department of of Obstetrics & Gynaecology M.K.C.G.Medical College Berhampur, Orissa, 760004, India

    2. 30/08/2002 Antioxidants in Obstetrics and Gynaecology - Prof.S.N.Panda & Dr.Sasmita Das 2 Introduction

    3. 30/08/2002 Antioxidants in Obstetrics and Gynaecology - Prof.S.N.Panda & Dr.Sasmita Das 3 Free Radicals (FRs) These are highly reactive chemical entities that have a single unpaired electron in their outer most orbit. Under certain conditions can be highly toxic to the cells. Generally unstable and try to become stable, either by accepting or donating an electron. Therefore if two FRs react, they neutralise each other. However, if the FRs react with stable molecules, there is generation of more free radicals. This characteristic enables the FRs to participate in auto catalytic chain reactions, Molecules with which they react are themselves converted to free radicals to propagate the chain of damages.

    4. 30/08/2002 Antioxidants in Obstetrics and Gynaecology - Prof.S.N.Panda & Dr.Sasmita Das 4 Reactive Oxygen Species (ROS): - These are free radicals derived initially from oxygen. But as they do not contain unpaired electrons in their outermost orbit, they do not qualify as free radicals and so are referred to separately as ROS. Eg.- H2O2, HOCL, NO.

    5. 30/08/2002 Antioxidants in Obstetrics and Gynaecology - Prof.S.N.Panda & Dr.Sasmita Das 5 Physiological Stimuli that Form FRs Normal respiration – O2 – Superoxide, H2O2 – Hydrogen Peroxide HOCL – Hypochlorous acid NO – Nitric Oxide Transition metals present inside our body when are in free form behave as free radicals. Fe2+, Cu+ Body cells- Endothelium (NO3 – Nitric Oxide, NO2 – Nitrous Oxide), Macrophages (NO2) Neurones (ONOOH – Peroxy nitrite). Ageing Phagocytosis or biogenetics Oxidation of foods and endogenous compounds. Transportation of substances for energy production.

    6. 30/08/2002 Antioxidants in Obstetrics and Gynaecology - Prof.S.N.Panda & Dr.Sasmita Das 6 Pathological Stimuli that Form FRs Radiation ?Breaks the water inside our body: H2O =H+ + OH- Metabolism of drugs ? CCl3 Transition Metals ? Cu+, Fe2+ Ultraviolet rays Emotional stress

    7. 30/08/2002 Antioxidants in Obstetrics and Gynaecology - Prof.S.N.Panda & Dr.Sasmita Das 7 Actions of FRs Mechanism of Action: They act on the cell membranes and membranes of different organelles of cells and cause cell injury and death by oxidative reactions. So FRs are also called OXIDANTS.

    8. 30/08/2002 Antioxidants in Obstetrics and Gynaecology - Prof.S.N.Panda & Dr.Sasmita Das 8 Actions of FRs FRs cause lipid peroxidation. The PUFA of cell membrane are more vulnerable for this injury. By lipid peroxidation FR increases the permeability of cells, leading to calcium influx and altered PH of the cell. FRs alter the enzyme and receptor proteins. FRs cause – cross-linking of proteins and fragmentation of protein strands, oxidation of amino acids like cystene, Methionine. These alterations in the enzymes and receptoors inside the cell lead to abnormal cell behaviour.

    9. 30/08/2002 Antioxidants in Obstetrics and Gynaecology - Prof.S.N.Panda & Dr.Sasmita Das 9 Actions of FRs FRs cause fracturing on the cell nucleus resulting in single strand DNA damage. This oxidative injury may be. Lethal – Leading to cell death and ultimately removed by phagocytosis. Sub lethal - which may result in Increased cell permeability. Toxicity. Mutation of cells.

    10. 30/08/2002 Antioxidants in Obstetrics and Gynaecology - Prof.S.N.Panda & Dr.Sasmita Das 10 FRs Induce Chain Reaction During the process of oxidant damage resulting in tissue destruction & degeneration, some electrons may escape oxidation and become FRs This chain reaction may produce diseases like: - Carcinogenesis. Myocardial reperfusion injury. Shock related injury. Arteriosclerosis. Rheumatoid arthritis. Adult respiratory diseases. Diabetes. Obesity. Lipid abnormality. Etc.

    11. 30/08/2002 Antioxidants in Obstetrics and Gynaecology - Prof.S.N.Panda & Dr.Sasmita Das 11 Antioxidants (AOs) These are substances, which protect us against potentially harmful free radicals derived from oxygen. To combat the injurious effects of FRs our body has its own system of ‘in vivo’ Antioxidants’. In normal healthy state a balance is maintained between FRs & AOs The ‘AO’ activity of serum is measured as - % inhibition of lipid peroxidation in a standardised brain homogenate. Moreover we can as well supplement these from outside (in vitro Antioxidants).

    12. 30/08/2002 Antioxidants in Obstetrics and Gynaecology - Prof.S.N.Panda & Dr.Sasmita Das 12 In Vivo Antioxidants: -

    13. 30/08/2002 Antioxidants in Obstetrics and Gynaecology - Prof.S.N.Panda & Dr.Sasmita Das 13 In Vivo Antioxidants: - These are binding proteins. They keep the free ions of plasma in a binding form, so prevent oxidation injury. Eg.-Transferin for Fe, Ceruloplasmin for Cu

    14. 30/08/2002 Antioxidants in Obstetrics and Gynaecology - Prof.S.N.Panda & Dr.Sasmita Das 14 In Vivo Antioxidants: - Source Vitamin A, C & E, Cystine, Glutathion, Melthionine, Bioflavines, Se, Zn.

    15. 30/08/2002 Antioxidants in Obstetrics and Gynaecology - Prof.S.N.Panda & Dr.Sasmita Das 15 Oxidative Stress: - Under normal conditions body maintains an equilibrium between its own FR’s and Antioxidants. When this equilibrium breaks, a state called oxidation stress arises with in, due to ? FR formation or ? AO system.

    16. 30/08/2002 Antioxidants in Obstetrics and Gynaecology - Prof.S.N.Panda & Dr.Sasmita Das 16 AO Status in Normal Pregnancy: - There is increased need for AOs as there is increased production of FRs due to Pregnancy being a stressful condition. Because of the rapidly growing foetus there is increased cellular activity. Thus AO activity during normal pregnancy progressively increases as demonstrated by ? Serum tocopherol. ? Activity of GOP. ? Serum ceruloplasmin & transferring level. However, there is no evidence to suggest the need for administration of ‘AOs’ during normal pregnancy but drugs that lead to ‘FR’ formation must be avoided.

    17. 30/08/2002 Antioxidants in Obstetrics and Gynaecology - Prof.S.N.Panda & Dr.Sasmita Das 17 AOs & Diabetic Embryopathy: - Oxidative stress has been suggested to contribute to the increased risk of foetal malformations in poorly controlled diabetics. There are reports of ? lipid peroxidation in cell membranes in diabetic pregnancies Periods of maternal hyperglycaemia & hypoglycemia may cause marked changes in the availability of glucose to the foetus. Also ? conc. of lipids, notably the ketone bodies and branched chain amino acids in the maternal circulation contribute to altered nutrition for the embryo Leading to ? FR conc. & foetal malformation in embryo.

    18. 30/08/2002 Antioxidants in Obstetrics and Gynaecology - Prof.S.N.Panda & Dr.Sasmita Das 18 AOs & Diabetic Embryopathy: - During later part of pregnancy ? load of glucose in the mitochondria may accelerate the flow of electrons through respiratory chain including mitochondrial leakage of free radicals. This leads to ? production of FR in embryonic tissues to cause congenital malformations. Thus maintenance of normal concentration of metabolitetes of all nutrient class may be important for prevention of adverse foetal outcome. But the question is “ will dietary supplements alone hold the key to the future in diabetic embryopathy”? However, maintenance of blood glucose level at euglycemic level is always important for prevention of Diabetic embryopathy .

    19. 30/08/2002 Antioxidants in Obstetrics and Gynaecology - Prof.S.N.Panda & Dr.Sasmita Das 19 AOs & Down Syndrome: - Free radicals being the hallmark of aging, are greatly increased with ?maternal age. So FRs play a role in pathogenesis of Down’s syndrome. Administration of AOs may help in preventing this disease.

    20. 30/08/2002 Antioxidants in Obstetrics and Gynaecology - Prof.S.N.Panda & Dr.Sasmita Das 20 FRs & AOs in PIH : - Increased activity of free radicals promote maternal uterine vascular malformations. FRs are promoters of maternal vasoconstriction. O2 , H2 O2 & NO2 in combinations Inactivate the NO (a vasorelaxant) Causes ? PG synthatase activity. Produce peroxynitrate, a potent oxidant leading to the subsequent development of PIH (See also notes page). Evidence-. Lipid peroxide in pre-eclamptic placenta is about 1.8 times higher in comparison to normal placenta. Vit. E is less in serum of PIH patients. Severity of hypertension has been found to be inversely proportional to concentration of Vit. E. Pre eclampsia is an important cause of maternal morbidity & mortality and accounts for more then 40% of iatrogenic premature deliveries. Emergence of FRs as promoters of maternal vascular malformation:Pathogenesis: - The mechanisms involved in the initiation of the diseases are not clear. However it is associated with an Inadequate or shallow trophoblastic invasion of decidual spiral arterioles into a high-resistance low flow uteroplanental circulation. These inadequately dilated blood vessels in the placental bed remain non complaint to the signal for larger inflow of maternal blood into the inter villas space. This leads to placental ischemia & hypoxia. At this point most probably starts a most undesirable cycle of imbalance between FRs & Antioxidants leading to a oxidative state.Pre eclampsia is an important cause of maternal morbidity & mortality and accounts for more then 40% of iatrogenic premature deliveries. Emergence of FRs as promoters of maternal vascular malformation:Pathogenesis: - The mechanisms involved in the initiation of the diseases are not clear. However it is associated with an Inadequate or shallow trophoblastic invasion of decidual spiral arterioles into a high-resistance low flow uteroplanental circulation. These inadequately dilated blood vessels in the placental bed remain non complaint to the signal for larger inflow of maternal blood into the inter villas space. This leads to placental ischemia & hypoxia. At this point most probably starts a most undesirable cycle of imbalance between FRs & Antioxidants leading to a oxidative state.

    21. 30/08/2002 Antioxidants in Obstetrics and Gynaecology - Prof.S.N.Panda & Dr.Sasmita Das 21 FRs & AOs in Preterm Delivery: - Sub clinical chorioamnionitis leads to liberation of bacterial antitoxins (polysaccharide in nature) and inflammatory cytokines. These cause stimulation of inflammatory cells and cells of CX. which in turn produce NO2. Evidence: There is ? N2O in vaginal samples of females having preterm delivery. So antioxidants may play a part in the treatment of preterm delivery.

    22. 30/08/2002 Antioxidants in Obstetrics and Gynaecology - Prof.S.N.Panda & Dr.Sasmita Das 22 FRs & AOs in New Born Babies: - In recent years experimental and clinical data have provided compelling evidences for involvement of oxygen derived ‘FRs’ in disorders of prematurity. Chronic lung disease Retinopathy Intra ventricular haemorrhages. Necrotising Enterocolitis: - FRs cause microvascular injury and ? cell permeability leading to necrotising enterocolitis.

    23. 30/08/2002 Antioxidants in Obstetrics and Gynaecology - Prof.S.N.Panda & Dr.Sasmita Das 23 FRs & AOs in New Born Babies: - PDA: - ? Hypoxanthine radical in NBB leads to ? formation of PGE2 and causes PDA.  Kwashiorkor: - Studies suggest that kwashiorkor babies have ?FRs in their body . ?‘AO’ in Kwashiorkor babies are due to deficiency of Vit. A, E, C, Inositol & Selinium. Ideally the future treatment of Neonates with all these disease should include AO therapy.

    24. 30/08/2002 Antioxidants in Obstetrics and Gynaecology - Prof.S.N.Panda & Dr.Sasmita Das 24 Carcinogenesis: - Basics of cancer formation: - A normal cell can undergo malignant transformation in presence of procarcinogens and carcinogens. However, in early stages, it can revert back to normal cell when detected and corrected by our body immune system. Without immune system detection a normal cell is converted to malignant cell in stages – Initiation ? Promotion ? Progression

    25. 30/08/2002 Antioxidants in Obstetrics and Gynaecology - Prof.S.N.Panda & Dr.Sasmita Das 25 FRs in Carcinogenesis: - Free radicals are formed from stimulants like –Radiation, Xenobiotics, Inflammatory cells, Respiration etc, which act on cellular targets to cause oxidant DNA damage in form of mutagenesis & clostogenesis, which cause: - Initiation of carcinogenesis by- Activation of protooncogens. Inactivation or loss of tumour suppresser genes. Normal cell becomes initiated cell. Procarcinogens are metabolically activated by FRs, which cause promotion and progression of these initiated cells to cancer Ultimately carcinogenesis sets in

    26. 30/08/2002 Antioxidants in Obstetrics and Gynaecology - Prof.S.N.Panda & Dr.Sasmita Das 26 FRs & AOs in Carcinogenesis: -

    27. 30/08/2002 Antioxidants in Obstetrics and Gynaecology - Prof.S.N.Panda & Dr.Sasmita Das 27 AOs in Cancer Prevention: - DEFENCE: - enzymes with antioxidant property cause first line of defence by: - Protecting the lipids and enzymes against oxidation ?Retarding the generation of free radicals ? Creating a balance of ‘AOs’ against FRs in the body ? PREVENTS : - Cell pathology. Metabolic disturbances. Changes in cell permeability. Eormation of toxic products. ? Prevention of initiation of Carcinogenesis

    28. 30/08/2002 Antioxidants in Obstetrics and Gynaecology - Prof.S.N.Panda & Dr.Sasmita Das 28 AOs in Cancer Prevention: - INTERVENTION at promotion & progression stages: Local deactivation of genotoxins responsible for further nuclear mutations Inactivation of tumour promoters eg.- activation of granulocytes. Simulate oxygen. Maintenance of proper function of gap junction communication. Maintenance of physical stability of membrane & also within cells.

    29. 30/08/2002 Antioxidants in Obstetrics and Gynaecology - Prof.S.N.Panda & Dr.Sasmita Das 29 AOs in Cancer Prevention: - Majority of epidemiological data suggest supplementation with antioxidants- Vit.- A, E, C; beta carotene & selenium, decreases the incidence of various cancers.

    30. 30/08/2002 Antioxidants in Obstetrics and Gynaecology - Prof.S.N.Panda & Dr.Sasmita Das 30 AOs in Cancer Prevention: -

    31. 30/08/2002 Antioxidants in Obstetrics and Gynaecology - Prof.S.N.Panda & Dr.Sasmita Das 31 FRs & AOs in Infertility - Male Various studies have suggested Conc. of Malon –di-Aldehyde (MDA) is inversely proportional to fertility in case of males. In asthenospermic and oligoasthenospermic males there is increased serum concentration of MDA. Even in normospermic males if there is ? concentration of MDA there is reduced fertility. Addition of vitamin E causes decreased concentration of MDA and improves fertility.

    32. 30/08/2002 Antioxidants in Obstetrics and Gynaecology - Prof.S.N.Panda & Dr.Sasmita Das 32 FRs & AOs in Infertility - Female FRs cause - Short luteal phase and LPDS. In IVF arrest the cell growth (div) at 2, 4, 8 cell stages Hamper the regulation of corpus luteum.  Addition of ‘AOs’ improves the results.

    33. 30/08/2002 Antioxidants in Obstetrics and Gynaecology - Prof.S.N.Panda & Dr.Sasmita Das 33 CONCLUSION

    34. 30/08/2002 Antioxidants in Obstetrics and Gynaecology - Prof.S.N.Panda & Dr.Sasmita Das 34 CONCLUSION

    35. 30/08/2002 Antioxidants in Obstetrics and Gynaecology - Prof.S.N.Panda & Dr.Sasmita Das 35

More Related