WRITE UPS - OBSTETRIC VASCULOPATHY - The Menace of Free Radicals &  Antioxidants in Obs & Gynecology




There was an era when people were worried about the disease processes and its treatment. But off late, tremendous efforts are being made to find out the ways of prevention of important diseases. The important research studies are rightly to be repeated with other populations, but nevertheless give an opportunity to consider the integrated actions of the known reducing (Antioxidant) systems. Inadequacy of certain internally produced reducing systems has been postulated as being at the core of some disease processes. It is believed that life has originated from basic chemicals by free radical reaction, largely initialed by ionizing radiation from sun. Paradoxically the same reactions creating life may also be responsible for many diseases, ageing and death.

 Free Radicals (FRs) 

These are highly reactive chemical entities that have a single unpaired electron in their outer most orbits. 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 neutralize 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 autocatalytic chain reactions,

Molecules with which they react are themselves converted to free radicals to propagate the chain of damages. 

 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. E.g.- H2O2, HOCL, NO.  Free radicals are formed in side our body by both PHYSIOLOGICAL (Natural) and PATHOLOGICAL stimuli.

 Mechanism of Action of FRs :

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. 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 receptors inside the cell lead to abnormal cell behavior. 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. It may also be sub lethal - which may result in increased cell permeability leading to mutation of cells. FRs Induce chain reactions 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.  

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 standardized brain homogenate. Moreover we can as well supplement these from outside (in vitro Antioxidants).

  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.

 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 fetus there is increased cellular activity. Thus AO activity during normal pregnancy progressively increases as demonstrated by Serum tocopherol. 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.

 AOs & Diabetic Embryopathy: - 

Oxidative stress has been suggested to contribute to the increased risk of fetal malformations in poorly controlled diabetics. There are reports of lipid peroxidation in cell membranes in diabetic pregnancies Periods of maternal hyperglycemia & hypoglycemia may cause marked changes in the availability of glucose to the fetus. 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. & fetal malformation in embryo.

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 metabolites of all nutrient class may be important for prevention of adverse fetal 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.

 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.

 FRs & AOs in Preterm Delivery: - 

Sub clinical chorioamnionitis leads to libe

ration 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.

 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 like Chronic lung disease, Retinopathy, Intra ventricular hemorrhages. Narcotizing Enterocolitis: - FRs cause microvascular injury and cell permeability leading to narcotizing enterocolitis.

 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. 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 proto-oncogens. Procarcinogens are metabolically activated by FRs, which cause promotion and progression of these initiated cells to cancer and ultimately carcinogenesis sets in

 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 and creating a balance of ‘AOs’ against FRs in the body prevents cell pathology, metabolic disturbances, changes in cell permeability, formation of toxic products and resultant prevention of initiation of carcinogenesis. Majority of epidemiological data suggest supplementation with antioxidants- Vit.- A, E, C; beta carotene & selenium, decreases the incidence of various cancers.

 FRs & AOs in Infertility - Male 

Various studies have suggested Conc. of Malondialdehyde (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.

 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.


Traffic lights are to cars, what ‘AOs’ are to the cells. Oxidant generation is a part of human life. Every O2 atom we breath in ,is converted to water inside our body by addition of four electrons sequentially. When four electrons are added three ‘FRs’- O2, H2 O2 & OH are formed along with water. So where there is life there are oxidants. But when produced in excess, they can cause any disease. So our concern should be to FRs in systemic circulation. However, careful use of ‘AOs’ and newer and more accurate methods to measure oxidant generation in humans will go a long way to find out the exact contribution of oxidants in disease processes and the role of ‘AOs’ to prevent it.



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