Antioxidant and Pro-oxidant Activities of Carotenoids

Living reference work entry
Part of the Reference Series in Phytochemistry book series (RSP)


Carotenoids are plant pigments widely spread in nature, especially in fruits and vegetables. These compounds have been subject of scientific research due to their several biological activities. Attention has been devoted to their role as antioxidants and/or pro-oxidants. If in one hand carotenoids are postulated to reduce the risk and prevent the development of several diseases associated with oxidative stress, including cancer, cardiovascular, and chronic diseases. On the other hand, due to their potential pro-oxidant action, carotenoids may enhance harmful effects and oxidative damage to biomolecules, like DNA, proteins, and membranes. This chapter provides a general overview of carotenoids and their mechanisms of action, both as anti- and/or pro-oxidants, as evaluated in in vitro non-cellular and cellular models as well as in in vivo systems.


Carotenes Xanthophylls Reactive species Antioxidant Pro-oxidant Oxidative stress 



2,2′-Azino-bis-(3-ethylbenzothiazoline-6-sulphonic acid)


2,2′-Azobis (2-methylpropionamidine)dihydrochloride




β-Carotene-9′,10′-oxigenase 2


Cluster determinant 36


2′,7′-Dichlorofluorescein diacetate

DHR 123

Dihydrorhodamine 123




Ferric reducing antioxidant power


Glutathione peroxidase




Glutathione S-transferase


Intermediate-density lipoprotein


Low-density lipoprotein




Oxygen-radical absorbance capacity


Oxygen radical absorbing capacity for lipophilic compounds




Reactive nitrogen species


Reactive oxygen species


Scavenger receptor class B member 1


Superoxide dismutase


Very low-density lipoprotein



This work received financial support from PT national funds (FCT/MCTES, Fundação para a Ciência e Tecnologia and Ministério da Ciência, Tecnologia e Ensino Superior) through grant UIDB/50006/2020 (LAQV-REQUIMTE Associate Laboratory) and from the European Union (FEDER funds through COMPETE POCI-01-0145-FEDER-029253). Marisa Freitas acknowledges the financial support from the European Union (FEDER funds through COMPETE POCI-01-0145-FEDER-029248).


  1. 1.
    Rao AV, Rao LG (2007) Carotenoids and human health. Pharmacol Res 55(3):207–216PubMedGoogle Scholar
  2. 2.
    Milani A, Basirnejad M, Shahbazi S, Bolhassani A (2017) Carotenoids: biochemistry, pharmacology and treatment. Br J Pharmacol 174(11):1290–1324PubMedGoogle Scholar
  3. 3.
    Nagao A (2014) Bioavailability of dietary carotenoids: intestinal absorption and metabolism. Jpn Agric Res Q 48(4):385–391Google Scholar
  4. 4.
    Walter MH, Strack D (2011) Carotenoids and their cleavage products: biosynthesis and functions. Nat Prod Rep 28(4):663–692Google Scholar
  5. 5.
    Fiedor J, Burda K (2014) Potential role of carotenoids as antioxidants in human health and disease. Nutrients 6(2):466–488PubMedPubMedCentralGoogle Scholar
  6. 6.
    El-Agamey A, Lowe GM, McGarvey DJ, Mortensen A, Phillip DM, Truscott TG, Young AJ (2004) Carotenoid radical chemistry and antioxidant/pro-oxidant properties. Arch Biochem Biophys 430(1):37–48PubMedGoogle Scholar
  7. 7.
    Palozza P (1998) Prooxidant actions of carotenoids in biologic systems. Nutr Rev 56(9):257–265PubMedGoogle Scholar
  8. 8.
    Shete V, Quadro L (2013) Mammalian metabolism of β-carotene: gaps in knowledge. Nutrients 5(12):4849–4868PubMedPubMedCentralGoogle Scholar
  9. 9.
    Ribeiro D, Freitas M, Silva AMS, Carvalho F, Fernandes E (2018) Antioxidant and pro-oxidant activities of carotenoids and their oxidation products. Food Chem Toxicol 120:681–699PubMedGoogle Scholar
  10. 10.
    Siems W, Wiswedel I, Salerno C, Crifò C, Augustin W, Schild L, Langhans C-D, Sommerburg O (2005) β-carotene breakdown products may impair mitochondrial functions – potential side effects of high-dose β-carotene supplementation. J Nutr Biochem 16(7):385–397PubMedGoogle Scholar
  11. 11.
    Jomova K, Valko M (2013) Health protective effects of carotenoids and their interactions with other biological antioxidants. Eur J Med Chem 70:102–110PubMedGoogle Scholar
  12. 12.
    Namitha KK, Negi PS (2010) Chemistry and biotechnology of carotenoids. Crit Rev Food Sci Nutr 50(8):728–760PubMedGoogle Scholar
  13. 13.
    Pérez-Gálvez A, Viera I, Roca M (2020) Carotenoids and chlorophylls as antioxidants. Antioxidants 9(6):1Google Scholar
  14. 14.
    Young AJ, Lowe GM (2001) Antioxidant and prooxidant properties of carotenoids. Arch Biochem Biophys 385(1):20–27PubMedPubMedCentralGoogle Scholar
  15. 15.
    Tapiero H, Townsend DM, Tew KD (2004) The role of carotenoids in the prevention of human pathologies. Biomed Pharmacother 58(2):100–110PubMedPubMedCentralGoogle Scholar
  16. 16.
    Esatbeyoglu T, Rimbach G (2017) Canthaxanthin: from molecule to function. Mol Nutr Food Res 61(6):1600469Google Scholar
  17. 17.
    Gammone MA, Riccioni G, D’Orazio N (2015) Marine carotenoids against oxidative stress: effects on human health. Mar Drugs 13(10):6226–6246PubMedPubMedCentralGoogle Scholar
  18. 18.
    Khachik F, Carvalho L, Bernstein PS, Muir GJ, Zhao D-Y, Katz NB (2002) Chemistry, distribution, and metabolism of tomato carotenoids and their impact on human health. Exp Biol Med 227(10):845–851Google Scholar
  19. 19.
    Priyadarshani AMB (2017) A review on factors influencing bioaccessibility and bioefficacy of carotenoids. Crit Rev Food Sci Nutr 57(8):1710–1717PubMedGoogle Scholar
  20. 20.
    Bohn T, Desmarchelier C, Dragsted LO, Nielsen CS, Stahl W, Rühl R, Keijer J, Borel P (2017) Host-related factors explaining interindividual variability of carotenoid bioavailability and tissue concentrations in humans. Mol Nutr Food Res 61(6):1600685PubMedCentralGoogle Scholar
  21. 21.
    Wu L, Guo X, Wang W, Medeiros DM, Clarke SL, Lucas EA, Smith BJ, Lin D (2016) Molecular aspects of β, β-carotene-9′, 10′-oxygenase 2 in carotenoid metabolism and diseases. Exp Biol Med 241(17):1879–1887Google Scholar
  22. 22.
    Burri BJ, La Frano MR, Zhu C (2016) Absorption, metabolism, and functions of β-cryptoxanthin. Nutr Rev 74(2):69–82PubMedPubMedCentralGoogle Scholar
  23. 23.
    Caris-Veyrat C, Schmid A, Carail M, Böhm V (2003) Cleavage products of lycopene produced by in vitro oxidations: characterization and mechanisms of formation. J Agric Food Chem 51(25):7318–7325PubMedGoogle Scholar
  24. 24.
    Burri BJ, Clifford AJ (2004) Carotenoid and retinoid metabolism: insights from isotope studies. Arch Biochem Biophys 430(1):110–119PubMedGoogle Scholar
  25. 25.
    Pisoschi AM, Pop A (2015) The role of antioxidants in the chemistry of oxidative stress: a review. Eur J Med Chem 97:55–74PubMedGoogle Scholar
  26. 26.
    Stahl W, Sies H (1996) Lycopene: a biologically important carotenoid for humans? Arch Biochem Biophys 336(1):1–9PubMedGoogle Scholar
  27. 27.
    Black HS, Boehm F, Edge R, Truscott TG (2020) The benefits and risks of certain dietary carotenoids that exhibit both anti- and pro-oxidative mechanisms-a comprehensive review. Antioxidants 9(3):264PubMedCentralGoogle Scholar
  28. 28.
    Nishino A, Maoka T, Yasui H (2016) Analysis of reaction products of astaxanthin and its acetate with reactive oxygen species using LC/PDA ESI-MS and ESR spectrometry. Tetrahedron Lett 57(18):1967–1970Google Scholar
  29. 29.
    Yang C, Zhang L, Zhang H, Sun Q, Liu R, Li J, Wu L, Tsao R (2017) Rapid and efficient conversion of all-E-astaxanthin to 9Z- and 13Z-isomers and assessment of their stability and antioxidant activities. J Agric Food Chem 65(4):818–826PubMedGoogle Scholar
  30. 30.
    Raposo MFJ, de Morais AMMB, de Morais RMSC (2015) Carotenoids from marine microalgae: a valuable natural source for the prevention of chronic diseases. Mar Drugs 13(8):5128–5155PubMedPubMedCentralGoogle Scholar
  31. 31.
    Chintong S, Phatvej W, Rerk-Am U, Waiprib Y, Klaypradit W (2019) In vitro antioxidant, antityrosinase, and cytotoxic activities of astaxanthin from shrimp waste. Antioxidants 8(5):128PubMedCentralGoogle Scholar
  32. 32.
    Miller NJ, Sampson J, Candeias LP, Bramley PM, Rice-Evans CA (1996) Antioxidant activities of carotenes and xanthophylls. FEBS Lett 384(3):240–242PubMedGoogle Scholar
  33. 33.
    Inoue Y, Shimazawa M, Nagano R, Kuse Y, Takahashi K, Tsuruma K, Hayashi M, Ishibashi T, Maoka T, Hara H (2017) Astaxanthin analogs, adonixanthin and lycopene, activate Nrf2 to prevent light-induced photoreceptor degeneration. J Pharmacol Sci 134(3):147–157PubMedGoogle Scholar
  34. 34.
    Lin C-W, Yang C-M, Yang C-H (2020) Protective effect of astaxanthin on blue light light-emitting diode-induced retinal cell damage via free radical scavenging and activation of PI3K/Akt/Nrf2 pathway in 661W cell model. Mar Drugs 18(8):387PubMedCentralGoogle Scholar
  35. 35.
    Hormozi M, Ghoreishi S, Baharvand P (2019) Astaxanthin induces apoptosis and increases activity of antioxidant enzymes in LS-180 cells. Artif Cells Nanomed Biotechnol 47(1): 891–895PubMedGoogle Scholar
  36. 36.
    Kumar A, Dhaliwal N, Dhaliwal J, Dharavath RN, Chopra K (2020) Astaxanthin attenuates oxidative stress and inflammatory responses in complete Freund-adjuvant-induced arthritis in rats. Pharmacol Rep 72(1):104–114PubMedGoogle Scholar
  37. 37.
    Cui G, Li L, Xu W, Wang M, Jiao D, Yao B, Xu K, Chen Y, Yang S, Long M, Li P, Guo Y (2020) Astaxanthin protects ochratoxin A-induced oxidative stress and apoptosis in the heart via the Nrf2 pathway. Oxidative Med Cell Longev 2020:7639109Google Scholar
  38. 38.
    Li L, Chen Y, Jiao D, Yang S, Li L, Li P (2020) Protective effect of astaxanthin on ochratoxin A-induced kidney injury to mice by regulating oxidative stress-related NRF2/KEAP1 pathway. Molecules 25(6):1386PubMedCentralGoogle Scholar
  39. 39.
    Li X, Matsumoto T, Takuwa M, Ali MSES, Hirabashi T, Kondo H, Fujino H (2020) Protective effects of astaxanthin supplementation against ultraviolet-induced photoaging in hairless mice. Biomedicine 8(2):18Google Scholar
  40. 40.
    Mordi RC, Walton JC (2016) Identification of products from canthaxanthin oxidation. Food Chem 197:836–840PubMedGoogle Scholar
  41. 41.
    Sen Gupta S, Ghosh M (2013) In vitro antioxidative evaluation of α- and β-carotene, isolated from crude palm oil. J Anal Methods Chem 2013:351671PubMedPubMedCentralGoogle Scholar
  42. 42.
    Panasenko OM, Sharov VS, Briviba K, Sies H (2000) Interaction of peroxynitrite with carotenoids in human low density lipoproteins. Arch Biochem Biophys 373(1):302–305PubMedGoogle Scholar
  43. 43.
    Boon CS, McClements DJ, Weiss J, Decker EA (2010) Factors influencing the chemical stability of carotenoids in foods. Crit Rev Food Sci Nutr 50(6):515–532PubMedGoogle Scholar
  44. 44.
    Sommerburg O, Langhans C-D, Arnhold J, Leichsenring M, Salerno C, Crifò C, Hoffmann GF, Debatin K-M, Siems WG (2003) β-Carotene cleavage products after oxidation mediated by hypochlorous acid – a model for neutrophil-derived degradation. Free Radic Biol Med 35(11):1480–1490PubMedGoogle Scholar
  45. 45.
    Mueller L, Boehm V (2011) Antioxidant activity of β-carotene compounds in different in vitro assays. Molecules 16(2):1055–1069PubMedGoogle Scholar
  46. 46.
    Kikugawa K, Hiramoto K, Tomiyama S, Asano Y (1997) β-Carotene effectively scavenges toxic nitrogen oxides: nitrogen dioxide and peroxynitrous acid. FEBS Lett 404(2–3):175–178PubMedGoogle Scholar
  47. 47.
    Trevithick-Sutton CC, Foote CS, Collins M, Trevithick JR (2006) The retinal carotenoids zeaxanthin and lutein scavenge superoxide and hydroxyl radicals: a chemiluminescence and ESR study. Mol Vis 12:1127–1135PubMedGoogle Scholar
  48. 48.
    Kennedy TA, Liebler DC (1992) Peroxyl radical scavenging by β-carotene in lipid bilayers. Effect of oxygen partial pressure. J Biol Chem 267(7):4658–4663PubMedGoogle Scholar
  49. 49.
    Everett SA, Dennis MF, Patel KB, Maddix S, Kundu SC, Willson RL (1996) Scavenging of nitrogen dioxide, thiyl, and sulfonyl free radicals by the nutritional antioxidant β-carotene. J Biol Chem 271(8):3988–3994PubMedGoogle Scholar
  50. 50.
    Chisté RC, Freitas M, Mercadante AZ, Fernandes E (2014) Carotenoids inhibit lipid peroxidation and hemoglobin oxidation, but not the depletion of glutathione induced by ROS in human erythrocytes. Life Sci 99(1):52–60PubMedGoogle Scholar
  51. 51.
    Ribeiro D, Sousa A, Nicola P, Ferreira de Oliveira JMP, Rufino AT, Silva M, Freitas M, Carvalho F, Fernandes E (2020) β-Carotene and its physiological metabolites: effects on oxidative status regulation and genotoxicity in in vitro models. Food Chem Toxicol 141:111392PubMedGoogle Scholar
  52. 52.
    Akkara PJ, Sabina EP (2020) Pre-treatment with beta carotene gives protection against nephrotoxicity induced by bromobenzene via modulation of antioxidant system, pro-inflammatory cytokines and pro-apoptotic factors. Appl Biochem Biotechnol 190(2):616–633PubMedGoogle Scholar
  53. 53.
    Quesada-Gómez JM, Santiago-Mora R, Durán-Prado M, Dorado G, Pereira-Caro G, Moreno-Rojas JM, Casado-Díaz A (2018) β-Cryptoxanthin inhibits angiogenesis in human umbilical vein endothelial cells through retinoic acid receptor. Mol Nutr Food Res 62(2):1700489Google Scholar
  54. 54.
    Sachindra NM, Sato E, Maeda H, Hosokawa M, Niwano Y, Kohno M, Miyashita K (2007) Radical scavenging and singlet oxygen quenching activity of marine carotenoid fucoxanthin and its metabolites. J Agric Food Chem 55(21):8516–8522PubMedGoogle Scholar
  55. 55.
    Zhang H, Tang Y, Zhang Y, Zhang S, Qu J, Wang X, Kong R, Han C, Liu Z (2015) Fucoxanthin: a promising medicinal and nutritional ingredient. Evid Based Complementary Altern Med 2015:723515–723515Google Scholar
  56. 56.
    Peng J, Yuan J-P, Wu C-F, Wang J-H (2011) Fucoxanthin, a marine carotenoid present in brown seaweeds and diatoms: metabolism and bioactivities relevant to human health. Mar Drugs 9(10):1806–1828PubMedPubMedCentralGoogle Scholar
  57. 57.
    Rajauria G, Foley B, Abu-Ghannam N (2017) Characterization of dietary fucoxanthin from Himanthalia elongata brown seaweed. Food Res Int 99:995–1001PubMedGoogle Scholar
  58. 58.
    Taira J, Sonamoto M, Uehara M (2017) Dual biological functions of a cytoprotective effect and apoptosis induction by bioavailable marine carotenoid fucoxanthinol through modulation of the Nrf2 activation in RAW264.7 macrophage cells. Mar Drugs 15(10):305PubMedCentralGoogle Scholar
  59. 59.
    Zeng J, Zhang Y, Ruan J, Yang Z, Wang C, Hong Z, Zuo Z (2018) Protective effects of fucoxanthin and fucoxanthinol against tributyltin-induced oxidative stress in HepG2 cells. Environ Sci Pollut Res 25(6):5582–5589Google Scholar
  60. 60.
    Zheng J, Tian X, Zhang W, Zheng P, Huang F, Ding G, Yang Z (2019) Protective effects of fucoxanthin against alcoholic liver injury by activation of Nrf2-mediated antioxidant defense and inhibition of TLR4-mediated inflammation. Mar Drugs 17(10):552PubMedCentralGoogle Scholar
  61. 61.
    Yang C, Fischer M, Kirby C, Liu R, Zhu H, Zhang H, Chen Y, Sun Y, Zhang L, Tsao R (2018) Bioaccessibility, cellular uptake and transport of luteins and assessment of their antioxidant activities. Food Chem 249:66–76PubMedGoogle Scholar
  62. 62.
    Lakshminarayana R, Sathish UV, Dharmesh SM, Baskaran V (2010) Antioxidant and cytotoxic effect of oxidized lutein in human cervical carcinoma cells (HeLa). Food Chem Toxicol 48(7):1811–1816PubMedGoogle Scholar
  63. 63.
    Lakshminarayana R, Aruna G, Sathisha UV, Dharmesh SM, Baskaran V (2013) Structural elucidation of possible lutein oxidation products mediated through peroxyl radical inducer 2,2′-azobis (2-methylpropionamidine) dihydrochloride: antioxidant and cytotoxic influence of oxidized lutein in HeLa cells. Chem Biol Interact 203(2):448–455PubMedGoogle Scholar
  64. 64.
    Sindhu ER, Preethi KC, Kuttan R (2010) Antioxidant activity of carotenoid lutein in vitro and in vivo. Indian J Exp Biol 48(8):843–848PubMedGoogle Scholar
  65. 65.
    El-Kholy AA, Elkablawy MA, El-Agamy DS (2017) Lutein mitigates cyclophosphamide induced lung and liver injury via NF-κB/MAPK dependent mechanism. Biomed Pharmacother 92:519–527PubMedGoogle Scholar
  66. 66.
    Li H, Huang C, Zhu J, Gao K, Fang J, Li H (2018) Lutein suppresses oxidative stress and inflammation by Nrf2 activation in an osteoporosis rat model. Med Sci Monit 24:5071–5075PubMedPubMedCentralGoogle Scholar
  67. 67.
    Turkler C, Kulhan NG, Ata N, Kiremitli T, Cimen FK, Suleyman H (2018) The ameliorative effect of lutein on ovarian ischemia-reperfusion injury in rats. Bratisl Lek Listy 119(11): 713–717PubMedGoogle Scholar
  68. 68.
    Sies H, Stahl W (1998) Lycopene: antioxidant and biological effects and its bioavailability in the human. Proc Soc Exp Biol Med 218(2):121–124PubMedGoogle Scholar
  69. 69.
    Sun X, Jia H, Xu Q, Zhao C, Xu C (2019) Lycopene alleviates H2O2-induced oxidative stress, inflammation and apoptosis in bovine mammary epithelial cells via the NFE2L2 signaling pathway. Food Funct 10(10):6276–6285PubMedGoogle Scholar
  70. 70.
    Karaca A, Yilmaz S, Kaya E, Altun S (2019) The effect of lycopene on hepatotoxicity of aflatoxin B1 in rats. Arch Physiol Biochem 1–8. Online ahead of printGoogle Scholar
  71. 71.
    Xu F, Wang P, Yao Q, Shao B, Yu H, Yu K, Li Y (2019) Lycopene alleviates AFB1-induced immunosuppression by inhibiting oxidative stress and apoptosis in the spleen of mice. Food Funct 10(7):3868–3879PubMedGoogle Scholar
  72. 72.
    Abdel-Rahman HG, Abdelrazek HMA, Zeidan DW, Mohamed RM, Abdelazim AM (2018) Lycopene: hepatoprotective and antioxidant effects toward bisphenol A-induced toxicity in female wistar rats. Oxid Med Cell Longev 2018:5167524PubMedPubMedCentralGoogle Scholar
  73. 73.
    Celik H, Kucukler S, Ozdemir S, Comakli S, Gur C, Kandemir FM, Yardim A (2020) Lycopene protects against central and peripheral neuropathy by inhibiting oxaliplatin-induced ATF-6 pathway, apoptosis, inflammation and oxidative stress in brains and sciatic tissues of rats. Neurotoxicology 80:29–40PubMedGoogle Scholar
  74. 74.
    Scheidegger R, Pande AK, Bounds PL, Koppenol WH (1998) The reaction of peroxynitrite with zeaxanthin. Nitric Oxide 2(1):8–16PubMedGoogle Scholar
  75. 75.
    El-Akabawy G, El-Sherif NM (2019) Zeaxanthin exerts protective effects on acetic acid-induced colitis in rats via modulation of pro-inflammatory cytokines and oxidative stress. Biomed Pharmacother 111:841–851PubMedGoogle Scholar
  76. 76.
    Rahal A, Kumar A, Singh V, Yadav B, Tiwari R, Chakraborty S, Dhama K (2014) Oxidative stress, prooxidants, and antioxidants: the interplay. Biomed Res Int 2014:761264PubMedPubMedCentralGoogle Scholar
  77. 77.
    Eghbaliferiz S, Iranshahi M (2016) Prooxidant activity of polyphenols, flavonoids, anthocyanins and carotenoids: updated review of mechanisms and catalyzing metals. Phytother Res 30(9):1379–1391PubMedGoogle Scholar
  78. 78.
    Edge R, Truscott TG (1997) Prooxidant and antioxidant reaction mechanisms of carotene and radical interactions with vitamins E and C. Nutrition 13(11–12):992–994PubMedGoogle Scholar
  79. 79.
    Shin J, Song M-H, Oh J-W, Keum Y-S, Saini RK (2020) Pro-oxidant actions of carotenoids in triggering apoptosis of cancer cells: a review of emerging evidence. Antioxidants 9(6):1–17Google Scholar
  80. 80.
    Siems W, Sommerburg O, Schild L, Augustin W, Langhans C-D, Wiswedel I (2002) Beta-carotene cleavage products induce oxidative stress in vitro by impairing mitochondrial respiration. FASEB J 16(10):1289–1291PubMedGoogle Scholar
  81. 81.
    Palozza P, Serini S, Di Nicuolo F, Piccioni E, Calviello G (2003) Prooxidant effects of β-carotene in cultured cells. Mol Asp Med 24(6):353–362Google Scholar
  82. 82.
    Arathi BP, Sowmya PR-R, Kuriakose GC, Vijay K, Baskaran V, Jayabaskaran C, Lakshminarayana R (2016) Enhanced cytotoxic and apoptosis inducing activity of lycopene oxidation products in different cancer cell lines. Food Chem Toxicol 97:265–276PubMedGoogle Scholar

Authors and Affiliations

  1. 1.LAQV, REQUIMTE, Laboratory of Applied Chemistry, Department of Chemical Sciences, Faculty of PharmacyUniversity of PortoPortoPortugal
  2. 2.UCIBIO, REQUIMTE, Laboratory of Toxicology, Department of Biological Sciences, Faculty of PharmacyUniversity of PortoPortoPortugal

Section editors and affiliations

  • K. G. Ramawat
    • 1
  1. 1.Department of BotanyUniversity College of Science, M. L. Sukhadia UniversityUdaipurIndia

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