Open access

Introductory Chapter: Free Radicals and Lipid Peroxidation

Written By

Mahmoud Ahmed Mansour

Submitted: 11 September 2019 Published: 22 January 2020

DOI: 10.5772/intechopen.90057

From the Edited Volume

Lipid Peroxidation Research

Edited by Mahmoud Ahmed Mansour

Chapter metrics overview

879 Chapter Downloads

View Full Metrics

1. Introduction

During cellular metabolism, a potentially dangerous by-product named free radicals is liberated. They have several effects on cell survival, growth, and development and have remarkable effects in the pathogenesis of atherosclerosis, aging, development of cancer, and several other conditions including inflammatory diseases [1]. A free radical is characterized by containing in its outer orbit an unpaired electron [2]. During the process of adenosine triphosphate (ATP) production in the mitochondria, free radicals are generated by aerobic organisms. During the electron- transport steps of ATP production, due to the leakage of electrons from mitochondria, reactive oxygen species (ROS), superoxide anion (O2−∙) and hydroxyl (OH) radicals, are generated. These free radicals through chemical reactions can lead to the production of hydrogen peroxide (H2O2). Based on the presence of Fe2+ ions, hydroxyl radicals are produced [3].

Free radicals are involved in several beneficial and harmful actions. Free radicals are involved in the signal transduction pathways that regulate cell growth [4] and reduction-oxidation (redox) status [3] and have a vital role in the defense polymorph nuclear leukocytes against infections as it acts as the first line of defense [5]. However, free radicals in excessive amounts can induce lethal chain reactions, leading to inhibition and inactivation of vital enzymes and many other proteins which are important subcellular elements needed for cell survival and leading to apoptosis [6]. Thus, functionally free radicals are considered a double-edged sword (Figure 1).

Figure 1.

ROS, oxidative damage, and human diseases. Interrelationship between the effect of imbalance in the reactive oxygen species (ROS) and their consequences on the cellular growth and the cellular function leads to DNA damage and mutation.

Reactive oxygen species include radicals such as superoxide (O2−∙), hydroxyl radical (HO), nitric oxide (NO), and non-radical species such as hydrogen peroxide (H2O2) and peroxynitrite (ONOO) [7].

Reactive oxygen species is produced both enzymatically and nonenzymatically. Enzymatic sources include NADPH oxidase located on the cell membrane of polymorphonuclear cells, macrophages and endothelial cells [8], and cytochrome P450-dependent oxygenases [9]. Irreversible conversion of xanthine dehydrogenase to xanthine oxidase by mitochondrial protease uses molecular oxygen as electron acceptor and produces remarkable amounts of both O2 and H2O2. Therefore it can provide another enzymatic source of both free radicals and also constitutes a source of OH. The production of O2 occurs nonenzymatically too via transfer of a single electrons to oxygen reduced coenzymes or prosthetic groups (e.g., flavins or iron sulfur clusters). Furthermore, previously reduced xenobiotics by certain enzymes (e.g., the anticancer agent Adriamycin or the herbicide paraquat) can also produce free radicals.


2. Role of oxidative stress in different diseases

The oxidative stress plays a role in the pathogenesis of different clinical conditions. Cancer diseases, diabetes mellitus, atherosclerosis, chronic inflammatory diseases, human immunodeficiency virus (HIV) infection (AIDS), ischemia–reperfusion injury, and sleep apnea are important examples. The previously mentioned disease can be classified into two categories [10]. In the first category, a pro-oxidative shift in the systemic thiol/disulfide redox state is in parallel with impaired glucose clearance, suggesting that the mitochondria of the skeletal muscle may be the primary site of elevated ROS production; these conditions may be referred to as “mitochondrial oxidative stress” which is clearly in diabetes mellitus and cancer [11]. The second category is based on excessive stimulation of NADPH oxidase activity by cytokines or other agents and therefore refers to “inflammatory oxidative conditions.” In this case, elevated free radical levels or alteration of intracellular glutathione levels is often associated with pathological changes indicative of a dysregulation of signal transduction and/or gene expression, represented by a change in the expression of cell adhesion molecules [12].


3. Lipid peroxidation and incidence of cancers

There is clear evidence supporting the role of lipid peroxidation in the induction of selected human cancers, including the kidney, liver, and skin. Estrogen treatment induces lipid peroxidation and subsequently increases the incidence of renal cell cancer in experimental models [13, 14]. Based on this mechanism, it has been hypothesized that estrogen increases breast cancer risk as lipid peroxidation may be one mechanism [15]. But estrogen induces renal cancer or liver cancer in this experimental model, not breast cancer.

In contrast, there is evidence favoring lipid peroxidation as an anticarcinogenic mechanism in breast cancer. It has been confirmed that higher level of lipid peroxidation is usually associated with lower rate of cell proliferation. Therefore, there is an inverse relationship between the concentrations of lipid peroxides and the rate of the cell proliferation [16]. This is supported by the observation that tumor cells are more resistant to lipid peroxidation than normal cells [17]; indeed, it was shown that in hepatomas, the higher the growth rate of the tumor, the lower the microsomal phospholipid content and the degree of fatty acid unsaturation [16]. Hosmark and Lystad [18] have also reported that low levels of polyunsaturated fatty acids and cytochrome P450 and elevated levels of lipid-soluble antioxidant alpha-tocopherol in the hepatoma cells are the main causes behind lower rate of lipid peroxidation.

It has been reported that lipid peroxidation represents a protective mechanism in breast cancer. Decreased plasma malondialdehyde (MDA), which is a marker for lipid peroxidation, has been significantly associated with severity of prognosis factors for breast cancer. A significant lower plasma level of MDA was detected in patients with large tumors or in whom nodes and/or metastasis was present [19, 20].


  1. 1. Milisav I, Ribarič S, Poljsak B. Antioxidant vitamins and ageing. Sub-Cellular Biochemistry. 2018;90:1-23
  2. 2. Boveris A. Biochemistry of free radicals: From electrons to tissues. Medicina (B Aires). 1998;58(4):350-356
  3. 3. Cleveland JL, Kastan MB. Cancer. A radical approach to treatment. Nature. 2000;407(6802):309-311
  4. 4. Shukla S, Mishra R. Level of hydrogen peroxide affects expression and sub-cellular localization of Pax6. Molecular Biology Reports. 2018;45(4):533-540
  5. 5. Gizinger OA, Korkmazov AM, Sumerkina VA. Functional activity of neutrophils and local manifestations of oxidative stress in the mucous membrane of the nasal cavity in the early postoperative period. Vestnik Otorinolaringologii. 2019;84(2):40-45
  6. 6. Singh A, Kukreti R, Saso L, Kukreti S. Oxidative stress: A key modulator in neurodegenerative diseases. Molecules. 2019;24(8)
  7. 7. Elsner J, Kapp A. Reactive oxygen release. Methods in Molecular Biology. 2000;138:153-156
  8. 8. Jones OT. The regulation of superoxide production by the NADPH oxidase of neutrophils and other mammalian cells. BioEssays. 1994;16(12):919-923
  9. 9. Cassagnes LE, Perio P, Ferry G, Moulharat N, Antoine M, Gayon R, et al. In cellulo monitoring of quinone reductase activity and reactive oxygen species production during the redox cycling of 1,2 and 1,4 quinones. Free Radical Biology & Medicine. 2015;89:126-134
  10. 10. Ramos-Tovar E, Muriel P. Free radicals, antioxidants, nuclear factor-E2-related factor-2 and liver damage. Journal of Applied Toxicology. 2019
  11. 11. Białas AJ, Sitarek P, Miłkowska-Dymanowska J, Piotrowski WJ, Górski P. The role of mitochondria and oxidative/antioxidative imbalance in pathobiology of chronic obstructive pulmonary disease. Oxidative Medicine and Cellular Longevity. 2016;2016:7808576
  12. 12. Lenz AG, Karg E, Brendel E, Hinze-Heyn H, Maier KL, Eickelberg O, et al. Inflammatory and oxidative stress responses of an alveolar epithelial cell line to airborne zinc oxide nanoparticles at the air-liquid interface: A comparison with conventional, submerged cell-culture conditions. BioMed Research International. 2013;2013:652632
  13. 13. Gago-Dominguez M, Castelao JE, Yuan JM, Ross RK, Yu MC. Lipid peroxidation: A novel and unifying concept of the etiology of renal cell carcinoma (United States). Cancer Causes & Control. 2002;13:287-293
  14. 14. Gago-Dominguez M, Castelao JE. Lipid peroxidation and renal cell carcinoma: Further supportive evidence and new mechanistic insights. Free Radical Biology & Medicine. 2006;40:721-733
  15. 15. Gago-Dominguez M, Castelao JE, Pike MC, Sevanian A, Haile RW. Role of lipid peroxidation in the epidemiology and prevention of breast cancer. Cancer Epidemiology, Biomarkers & Prevention. 2005;14:2829-2839
  16. 16. Chajes V, Sattler W, Stranzl A, Kostner GM. Influence of n-3 fatty acids on the growth of human breast cancer cells in vitro: Relationship to peroxides and vitamin-E. Breast Cancer Research and Treatment. 1995;34:199-212
  17. 17. Gago-Dominguez M, Castelao JE, Sun CL, Van Den Berg D, Koh WP, Lee HP, et al. Marine n-3 fatty acid intake, glutathione S-transferase polymorphisms and breast cancer risk in postmenopausal Chinese women in Singapore. Carcinogenesis. 2004;25:2143-2147
  18. 18. Høstmark AT, Lystad E. Growth inhibition of human hepatoma cells (HepG2) by polyunsaturated fatty acids. Protection by albumin and vitamin E. Acta Physiologica Scandinavica. 1992;144(1):83-88
  19. 19. Saintot M, Astre C, Pujol H, Gerber M. Tumor progression and oxidant-antioxidant status. Carcinogenesis. 1996;17:1267-1271
  20. 20. Gerber M, Astre C, Segala C, Saintot M, Scali J, Simony-Lafontaine J, et al. Tumor progression and oxidant-antioxidant status. Cancer Letters. 1997;114:211-214

Written By

Mahmoud Ahmed Mansour

Submitted: 11 September 2019 Published: 22 January 2020