Antioxidant Vitamins Are Correlated with Different Aspects of Phagocytic Processes in Healthy Nigerians: Benefits As Supplements During Antimicrobial Treatment
Background: Antioxidant vitamins are important for the immune system to function efficiently through several mechanisms. However, according to several previous studies, individual step of leucocyte phagocytosis is not correlated with different antioxidant vitamins.
Methods: This study included 50 healthy Nigerians whose cellular phagocytic mechanism such as percentage leucocyte migration (%LM) and intracellular killing (%Nitroblue Tetrazolium Test) were determined by microscopy, neutrophil chemokines [plasma interleukin 8 (IL-8)] was determined using ELISA, and respiratory burst indices [plasma catalase (CAT), superoxide dismutase (SOD), myeloperoxidase (MPO), hydrogen peroxide (H2O2), and nitric oxide (NO)] were determined by spectrophotometry. While the plasma antioxidant vitamins (Vitamins A, C, and E) were determined using HPLC, the phagocytic indices, chemokines, and respiratory burst indices were correlated with plasma antioxidant vitamins using Spearman’s Correlation analysis at α0.05.
Results: The results show that although among the healthy Nigerian adults, vitamin C was significantly and positively correlated with %NBT, it was negatively correlated with CAT activity. Vitamin A showed a significantly positive correlation with SOD while Vitamin E showed a significantly negative correlation with MPO.
Conclusions: These findings suggest that antioxidant vitamins affect different stages of phagocytosis. It is advisable to use a combination of antioxidant vitamins as supplements with recommended treatment strategies against intracellular micro-organisms or inflammatory diseases.
Keywords: Antioxidants, Intracellular microbial killing, Vitamins
1. EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA). (2016). Guidance on the scientific requirements for health claims related to the immune system, the gastrointestinal tract and defence against pathogenic microorganisms. Efsa J. 14:4369.
2. Aderem A, Underhill DM. (1999). Mechanisms of phagocytosis in macrophages. Annu Rev Immunol. 17: 593-623
3. Winterbourn C.C., Kettle A.J., Hampton M.B. (2016). Reactive oxygen species and neutrophil function. Annu. Rev. Biochem. 85:765–792.
4. Del Rio M, Ruedas G, Medina S, Victor VM, De la Fuente. M. (1998). Improvement by several antioxidants of macrophage function in vitro. Life Sci. 63: 871- 881
5. Hoglen NC, Abril EA, Sauer JM, et al. (1997). Modulation of Kupffer cell and peripheral blood monocyte activity by in vivo treatment of rats with all-trans-retinol, Liver. 17: 157-165.
6. de la Fuente M, Ferrandez MD, Burgos MS, Soler A, Prieto A, Miquel J. (1998). Immune function in aged women is improved by ingestion of vitamins C and E. Canad J Physiol Pharmacol. 76: 373-380
7. Sureda A, Ferrer MD, Mestre A, Tur JA, Pons A. (2013). Prevention of neutrophil protein oxidation with vitamins C and E diet supplementation without affecting the adaptive response to exercise. Intl J Sport Nutr Exerc Metab. 23(1):31-39.
8. Alvarado C, Alvarez P, Puerto M, Gausserès N, Jiménez L, De la Fuente M. (2006). Dietary supplementation with antioxidants improves functions and decreases oxidative stress of leukocytes from prematurely aging mice. Nutrition. 22(7-8):767-777.
9. Wintergerst ES, Maggini S, Hornig DH. (2006). Immune-enhancing role of vitamin C and zinc and effect on clinical conditions. Ann Nutr Metab. 50(2):85-94.
10. Shrestha S., Kim S.Y., Yun Y.J., Kim J.K., Lee J.M., Shin M., Song D.K., Hong C.W.(2017). Retinoic acid induces hypersegmentation and enhances cytotoxicity of neutrophils against cancer cells. Immunol. Lett. 182:24–29.
11. Vellozo N.S., Pereiramarques S.T., Cabralpiccin M.P., Filardy A.A., Ribeirogomes F.L., Rigoni T.S., Dosreis G.A., Lopes M.F. (2017). All-trans retinoic acid promotes an m1- to m2-phenotype shift and inhibits macrophage-mediated immunity to leishmania major. Front. Immunol. 8:1560.
12. Kiss I., Rühl R., Szegezdi E., Fritzsche B., Toth B., Pongrácz J., Perlmann T., Fésüs L., Szondy Z. (2008). Retinoid receptor-activating ligands are produced within the mouse thymus during postnatal development. Eur. J. Immunol. 38:147–155.
13. Wu D, Han SN, Meydani M, Meydani SN. (2006). Effect of concomitant consumption of fish oil and vitamin E on T cell mediated function in the elderly: a randomized double-blind trial. J Am Coll Nutr. 25(4):300-306.
14. De la Fuente M , Hernanz A , Guayerbas N et al. (2008). Vitamin E ingestion improves several immune functions in elderly men and women. Free Radic Res. 42:272-280
15. Edem V.F and Arinola O.G (2015). Leucocyte migration and intracellular killing in newly diagnosed pulmonary tuberculosis patients and during anti-tuberculosis chemotherapy. Annals of Global Health. 81(5): 669-674.
16. Arinola O. G, Morenikeji O. A, Akinwande K. S, Alade A. O, Olateru-Olagbegi O, Alabi P. E, Rahamon S.K (2015). Serum levels of cytokines and IgE in Helminth-infected Nigerian Pregnant women and Children. Annals of Global Health. 81(5): 689-693.
17. Edem VF, Ige OM and Arinola OG. (2016). Plasma vitamins and essential trace elements in multi-drug resistant pulmonary tuberculosis patients before and during chemotherapy. Egyptian Journal of Chest Diseases and Tuberculosis. 65(2): 441-445.
18. Rytter M.J., Kolte L., Briend A., Friis H., Christensen V.B. (2014). The Immune System in Children with Malnutrition—A Systematic Review. PLoS ONE. 9:e105017.
19. Tan P.H., Sagoo P., Chan C., Yates J.B., Campbell J., Beutelspacher S.C., Foxwell B.M., Lombardi G., George A.J.( Inhibition of NF-kappa B and oxidative pathways in human dendritic cells by antioxidative vitamins generates regulatory T cells. J. Immunol. 2005;174:7633–7644.
20. Lammermann T. (2016). In the eye of the neutrophil swarm-navigation signals that bring neutrophils together in inflamed and infected tissues. J. Leukoc. Biol. 100:55–63.
21. Twining SS, Schulte DP, Wilson PM, Fish BL, Moulder JE. (1997). Vitamin A deficiency alters rat neutrophil function. J Nutr. 127; 558-565
22. Blass S.C., Goost H., Tolba R.H., Stoffel-Wagner B., Kabir K., Burger C., Stehle P., Ellinger S. (2012). Time to wound closure in trauma patients with disorders in wound healing is shortened by supplements containing antioxidant micronutrients and glutamine: A PRCT. Clin. Nutr. 31:469–475
23. Martin P., Leibovich S.J. (2005). Inflammatory cells during wound repair: The good, the bad and the ugly. Trends Cell Biol. 15:599–607.
24. Amitromach E., Uni Z., Cheled S., Berkovich Z., Reifen R. (2009). Bacterial population and innate immunity-related genes in rat gastrointestinal tract are altered by vitamin A-deficient diet. J. Nutr. Biochem. 20:70–77.
25. Prasanthi K and Rajini PS. (2005). Morphological and biochemical perturbations in rat erythrocytes following in vitro exposure to Fenvalerate and its metabolite. Toxicol In Vitro. 19:449–456.
26. Ruas CB, Carvalho Cdos S, de Araújo HS, Espíndola EL, Fernandes MN. (2008). Oxidative stress biomarkers of exposure in the blood of cichlid species from a metal-contaminated river. Ecotoxicol Environ Saf. 71:86–93.
27. Hemilä H.(2017).Vitamin C and infections. Nutrients. 9:339.doi:10.3390/nu9040339
28. Hemilä H , Louhiala P. Vitamin C for preventing and treating pneumonia. Cochrane Database Syst Rev 2013:CD005532.doi:10.1002/14651858.CD005532.pub3 pmid:http://www.ncbi.nlm.nih.gov/pubmed/23925826
29. Hemilä H , Chalker E. (2013).Vitamin C for preventing and treating the common cold. Cochrane Database Syst Rev 2013:CD000980.doi:10.1002/14651858.CD000980.pub4 pmid:http://www.ncbi.nlm.nih.gov/pubmed/23440782
30. Bakaev V.V., Duntau A.P. (2004). Ascorbic acid in blood serum of patients with pulmonary tuberculosis and pneumonia. Intl. J. Tuberc. Lung Dis. 8:263–266.
31. Bharara A., Grossman C., Grinnan D., Syed A.A., Fisher B.J., DeWilde C., Natarajan R., Fowler A.A. (2016). Intravenous vitamin C administered as adjunctive therapy for recurrent acute respiratory distress syndrome. Case Rep. Crit. Care. 2016:8560871.
32. Fowler A.A., Kim C., Lepler L., Malhotra R., Debesa O., Natarajan R., Fisher B.J., Syed A., DeWilde C., Priday A., et al. (2017). Intravenous vitamin C as adjunctive therapy for enterovirus/rhinovirus induced acute respiratory distress syndrome. World J. Crit. Care Med. 6:85–90.
33. Fisher B.J., Kraskauskas D., Martin E.J., Farkas D., Wegelin J.A., Brophy D., Ward K.R., Voelkel N.F., Fowler A.A., III, Natarajan R. (2012). Mechanisms of attenuation of abdominal sepsis induced acute lung injury by ascorbic acid. Am. J. Physiol. Lung Cell. Mol. Physiol. 303:L20–L32.
34. Wilgus T.A., Roy S., McDaniel J.C. (2013). Neutrophils and Wound Repair: Positive Actions and Negative Reactions. Adv. Wound Care. 2:379–388.
35. Carr A., Frei B. (1999). Does vitamin C act as a pro-oxidant under physiological conditions? FASEB J. 13:1007–1024.
36. Bergsten P., Amitai G., Kehrl J., Dhariwal K.R., Klein H.G., Levine M. (1990). Millimolar concentrations of ascorbic acid in purified human mononuclear leukocytes. Depletion and reaccumulation. J. Biol. Chem. 265:2584–2587.
37. Corpe C.P., Lee J.H., Kwon O., Eck P., Narayanan J., Kirk K.L., Levine M. (2005). 6-Bromo-6-deoxy-l-ascorbic acid: An ascorbate analog specific for Na+-dependent vitamin C transporter but not glucose transporter pathways. J. Biol. Chem. 280:5211–5220.
38. Buettner G.R. (1993). The pecking order of free radicals and antioxidants: Lipid peroxidation, alpha-tocopherol, and ascorbate. Arch. Biochem. Biophys. 300:535–543.
39. Bozonet SM and Carr AC (2019). The Role of Physiological Vitamin C oncentrations on Key Functions of Neutrophils Isolated from Healthy Individuals. Nutrients. 11(6): 1363.
40. Nusgens B.V., Humbert P., Rougier A., Colige A.C., Haftek M., Lambert C.A., Richard A., Creidi P., Lapiere C.M. (2001). Topically applied vitamin C enhances the mRNA level of collagens I and III, their processing enzymes and tissue inhibitor of matrix metalloproteinase 1 in the human dermis. J. Investig. Dermatol. 116:853–859.
41. Wu D , Meydani SN. (2004). Age-Associated changes in immune function: impact of vitamin E intervention and the underlying mechanisms. Endocr Metab Immune Disord Drug Targets.14:283–289.
42. Lee G, Han S. (2018). The role of vitamin E in immunity. Nutrients. 10:614
43. Meydani SN, Han SN, Wu D. (2005). Vitamin E and immune response in the aged: molecular mechanisms and clinical implications. Immunol Rev. 205:269–284.