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The Importance of Antioxidants in Cellular Response

- 5 min read
written by Shield Connect

Reactive oxygen species (ROS) can affect the normal cellular responses and oxidative stress (OS) can wreak havoc on the intracellular environment leading to cell death

Reactive oxygen species (ROS) can affect the normal cellular responses and oxidative stress (OS) can wreak havoc on the intracellular environment leading to cell death. When free radical generation and scavenging antioxidants are in equilibrium, reproductive cells and tissues become stable. The role of reactive oxygen species (ROS) has a strong impact on a range of physiological functions in the reproductive tract and high levels of ROS can lead to severe pathologies that impede ovulation and results in infertility. It is already evident that there is significant role of ROS in physiological processes including folliculogenesis, oocyte maturation, endometrial cycle, and implantation. Thereby antioxidants maintain all the above-mentioned processes.

Oxidative stress (OS):

An imbalance between prooxidant molecules produced by aerobic metabolism and defensive antioxidants causes oxidative stress1.

Antioxidant

Antioxidants are the molecule that prevents generation of the free radical inside the cells or scavenge existing free radicals that aid in the repair of ROS-induced damage to cell structures in normal conditions. Herein Vitamin C, vitamin E, zinc, selenium, beta carotene, taurine, hypotaurine, glutathione and cysteamine, are nonenzymatic antioxidants. SOD, catalase, GSH-Px, glutaredoxin, and glutathione reductase are examples of enzyme antioxidants2. The term ‘total antioxidant capacity’ is denoted as the amount of antioxidant defence present (TAC). Herein oral antioxidant supplementation may serve to prevent and alleviate oxidative damages to the cells which may results in pathogenesis of obstetrical disease including preeclampsia and recurrent pregnancy loss and gynecological disorders including polycystic ovarian syndrome (PCOS) or endometriosis.

The Importance of Antioxidants in Cellular Response Fig 1. The role of oxidative stress in obstetric and gynaecologic conditions that contribute to infertility1

Role in PCOS

Insulin resistance and hyperglycemia are established as factors that increase oxidative stress. Researchers have evaluated the effect of N-acetylcysteine (NAC), known to replenish stores of the antioxidant glutathione, on insulin secretion and peripheral insulin resistance in subjects with PCOS. Therefore, the antioxidant effects of NAC may serve as a therapeutic strategy to improve the level of circulating insulin and insulin sensitivity in PCOS patients with hyperinsulinemia. Further hemicalorimetry technique suggested that serum LPO and MDA in patients with PCOS were significantly higher than those found in normal women. Herein oralethinylestradiol and cyproterone acetate may alleviate the symptoms of PCOS through both its anti-androgenic and antioxidant actions3.

Role in Endometriosis

Adhesions, endometrioma, and pelvic anatomical anomalies are hypothesised to make a woman infertile by mechanically hindering the sperm-egg connection. The prooxidant/antioxidant balance may be disrupted by peritoneal fluid containing ROS-generating iron, macrophages, and environmental pollutants such as polychlorinated biphenyls, resulting in enhanced tissue proliferation and adhesions 4-5. Therefore, ROS are hypothesised to encourage endometrial cell proliferation and adhesion in the peritoneal cavity, contributing to the pelvic anatomical distortion that causes infertility in endometriosis patients. More recently, RU486- a potent antiprogesterone agent with antioxidant activity, has been shown to decrease the proliferation of epithelial and stromal cells in endometriosis. Curcumin is a polyphenol derived from turmeric with antioxidant property has been shown to have an anti-endometriotic effect by targeting aberrant matrix remodelling in a mouse model.MMP-9 also was identified as a therapeutic target in the treatment of OS-mediated endometriosis evaluating the effectiveness of melatonin in treating experimental endometriosis in a mouse model. The green tea-containing compound, epigallocatechin gallate (EGCG) has been evaluated as a treatment for endometriosis due to its powerful antioxidant and anti-angiogenic properties. Antioxidant supplementation was also observed to increase the activity of antioxidant enzymes (SOD and GPx), while decreasing markers of oxidative stress such as malondialdehyde and lipid peroxides6.

Role in unexplained Infertility

Elevated levels of ROS that disturb the redox balance within the body may be the root cause of infertility in women. The ovum released from the ovary, the zygote or embryo, and spermatozoa are very vulnerable to damage inflicted by OS. Treatment with 200 μg of oral selenium as selenomethionine and oral magnesium for a period of 2 months was shown to normalize RBC-Mg and RBC-GPx levels.

Use of antioxidants to promote healthy pregnancy

Preeclampsia

Reduced antioxidant response has been observed in patients with preeclampsia. Preeclampsia is associated with defective placentation, in which the dislodging of extravillous trophoblast plugs in the maternal spiral arteries leads to the onset of blood flow into the intervillous space, causing an oxidative burst that generates ROS. Early intervention at 16–22 weeks of pregnancy with supplementation of vitamin E and C resulted in significant reduction of preeclampsia7.

Recurrent Pregnancy Loss

In recurrent pregnancy loss oxidative stress may be implicated as placental oxidative stress that can lead to recurrent abortions by impairing placental development and causing trophoblast degeneration. The connection between recurrent pregnancy loss and OS is not only corroborated by the increase in ROS generation in early pregnancy but also can be related to increased levels of antioxidants needed to neutralize and scavenge excessive ROS in habitual abortion. Research suggested that elevated lipoperoxides and significantly decreased vitamin A, E, and beta carotene have been observed. Further nonenzymatic antioxidants, including vitamins C, E, and A, lycopenes, selenium compounds, lipoic acid, and ubiquinones8could scavenge ROS and ultimately prevent cellular damage. Homocysteine is a thiol-containing amino acid that is involved in the sulfurylation and methylation metabolic pathways and has been proposed to have pro-oxidant effects. Moreover Melatonin, a hormone that acts as a powerful agent against ROS, has been hypothesized to have properties essential for successful pregnancy and prevention of spontaneous abortion.

References:

  1. Lucky H. Sekhon et al., Female Infertility and Antioxidants, Current Women’s Health Reviews, 2010, 6, 84-95.
  2. Agarwal A, et al., Redox considerations in female reproductive function and assisted reproduction: from molecular mechanisms to health implications. Antioxid Redox Signal 2008; 10: 1376-88.
  3. Zhang D et al., The effects of oxidative stress to PCOS. 2008; 39(3): 421-3
  4. Arumugam K and Yip YC. De novo formation of adhesions in endometriosis: the role of iron and free radical reactions. FertilSteril 1995; 64(1): 62-4.
  5. Donnez Jet al. Current thinking on the pathogenesis of endometriosis. GynecolObstet Invest 2002; 54(Suppl. 1): 52-8; discussion 9-62.
  6. Mier-Cabrera J, Aburto-Soto T, Burrola-Mendez S, et al. Women with endometriosis improved their Peripherals antioxidants markers after the application of a high antioxidant diet. ReprodBiolEndocrinol 2009; 28(7): 54.
  7. Chappell LC, Seed PT, Briley AL, et al. Effect of antioxidants on the occurrence of pre-eclampsia in women at increased risk: a randomised trial. Lancet 1999; 354: 810-16.
  8. Sies H. Oxidative stress. Am J Med 1991; 91: 531-8.

Picture Credit :https://www.todaysparent.com/pregnancy/pregnancy-health/natural-heartburn-remedies-pregnancy

Dr. P. Prasanna Dr. Sayamstuti Pattanaik
MBBS, M.S (OBG)
Consultant Obstetrician and Gynaecologist,
Laparoscopic Surgeon and Infertility specialist
Shanti Memorial Hospital Rourkela, Odisha
.

 

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