Advertisement

Inflammation

, Volume 15, Issue 4, pp 303–315 | Cite as

Kojic acid scavenges free radicals while potentiating leukocyte functions including free radical generation

  • Yukie Niwa
  • Hirohiko Akamatsu
Original Articles

Abstract

The effects of kojic acid, a compound that suppresses melanogenesis and is widely consumed in the Japanese diet with the belief that it is beneficial to health, were investigated on several aspects of leukocyte function. Kojic acid significantly decreased the levels of reactive oxygen species (ROS) (O 2 ), H2O2, OH) generated by neutrophil and by a cell-free ROS-generating system. In contrast, it significantly enhanced neutrophil phagocytosis and ROS generation, and lymphocyte proliferation stimulated by phytohemagglutinin. In addition, calcium concentration, [Ca2+]i in human neutrophils was increased in the presence of kojic acid. These results suggest that kojic acid is a favorable agent in terms of host defense in that it enhances a number of activities of leukocytes, but scavenges ROS excessively released from cells or generated in the tissues or blood vessels that are potentially injurious to host tissues.

Keywords

Calcium H2O2 Reactive Oxygen Species Internal Medicine Free Radical 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Kensler, T. W., D. M. Bush, andW. J. Kozumbo. 1983. Inhibition of tumor promotion by a biomimetic superoxide dismutase.Science 221:75–77.Google Scholar
  2. 2.
    Nordenson, I., G. Beckman, andL. Beckman. 1976. The effect of Superoxide dismutase and catalase on radiation-induced chromosome breaks.Hereditas 82:125–126.Google Scholar
  3. 3.
    McCord, J. M., andR. S. Roy. 1982. The pathophysiology of superoxide: Role in inflammation and ischemia.Can. J. Physiol. 60:1346–1352.Google Scholar
  4. 4.
    Burton, K. P., J. M. McCord, andG. Ghai. 1984. Myocardial alterations due to free-radical generation.Am. J. Physiol. 247:H776-H783.Google Scholar
  5. 5.
    Yagi, K. 1984. Increased serum lipid peroxides initiate atherogenesis.Bio Essays 1:58–60.Google Scholar
  6. 6.
    Sasaguri, Y., M. Morimatsu, T. Kanoshita, T. Nakashima, T. Inagaki, andK. Yagi. 1985. Difference in susceptibility to injury by linoleic acid hydroperoxide between endothelial and smooth muscle cells of arteries.J. Appl. Biochem. 7:70–78.Google Scholar
  7. 7.
    Zigler, J. S., Jr., R. S. Bodaness, I. Gery, andJ. H. Kinoshita. 1981. Effects of lipid peroxidation products on the rat lens in organ culture: A possible mechanism of cataract initiation in retinal degenerative disease.Arch. Biochem. Biophys. 294:158–160.Google Scholar
  8. 8.
    Niwa, Y., S. Miyake, T. Sakane, M. Shingu, andM. Yokoyama. 1982. Auto-oxidative damage in Behçet's disease—endothelial cell damage following the elevated oxygen radicals generated by stimulated neutrophils.Clin. Exp. Immunol. 49:247–255.Google Scholar
  9. 9.
    Niwa, Y., andK. Sohmiya. 1984. Enhanced neutrophilic functions in mucocutaneous lymph node syndrome, with special reference to the possible role of increased oxygen intermediate generation in the pathogenesis of coronary thromboarteritis.J. Pediatr. 104:56–60.Google Scholar
  10. 10.
    Niwa, Y., T. Sakane, M. Shingu, andM. M. Yokoyama. 1983. Effect of stimulated neutrophils from the synovial fluid of patients with rheumatoid arthritis on lymphocytes—a possible role of increased oxygen radicals generated by the neutrophils.J. Clin. Immunol. 3:228–240.Google Scholar
  11. 11.
    Michelson, A. M. 1982. Oxygen radicals.Agents Actions (Suppl.) 11:179–201.Google Scholar
  12. 12.
    Niwa, Y., T. Kasama, Y. Miyachi, andT. Kanoh. 1989. Neutrophil chemotaxis, phagocytosis and parameters of reactive oxygen species in human aging: Cross-sectional and longitudinal studies.Life Sci. 44:1655–1664.Google Scholar
  13. 13.
    Niwa, Y., K. Somiya, A. M. Michelson, andK. Puget. 1985. Effect of liposomal-encapsulated superoxide dismutase on active oxygen-related human disorders. A preliminary study.Free Rad. Res. Commun. 1:137–153.Google Scholar
  14. 14.
    Baillet, F., M. Housset, A. M. Michelson, andK. Puget. 1986. Treatment of radiofibrosis with liposomal superoxide dismutase. Preliminary results of 50 cases.Free Rad. Res. Commun. 1:387–394.Google Scholar
  15. 15.
    Michelson, A. M., G. Jadot, andK. Puget. 1986. Treatment of brain trauma with liposomal superoxide dismutase.Free Rad. Res. Commun. 4:209–224.Google Scholar
  16. 16.
    Somiya, K., Y. Niwa, andA. M. Michelson. 1986. Effects of liposomal Superoxide dismutase on human neutrophil activity.Free Rod. Res. Commun. 1:329–337.Google Scholar
  17. 17.
    Niwa, Y., T. Kanoh, T. Kasama, andM. Negishi. 1988. Activation of antioxidant activity in natural medicinal products by heating, brewing, and lipophilization. A new drug delivery system.Drugs Exp. Clin. Res. 14:361–372.Google Scholar
  18. 18.
    Niwa, Y., andY. Miyachi. 1986. Antioxidant action of natural health products and Chinese herbs.Inflammation 10:79–91.Google Scholar
  19. 19.
    Ikawa, T., K. Takeda, T. Yamamoto, andC. Takahashi. 1982. Clinical effectiveness of kojic acid preparations.J. West Jpn. Dermatol. 44:470–473 (in Japanese).Google Scholar
  20. 20.
    Mishima, Y., S. Hatta, Y. Ohyama, andM. Inazu. 1988. Induction of melanogenesis suppression: Cellular pharmacology and mode of differential action.Pigment Cell Res. 1:367–374.Google Scholar
  21. 21.
    Niwa, Y., T. Sakane, S. Yamamoto, T. Kanoh, andS. Taniguchi. 1985. Methyltransferase and phospholipase A2 activity in membranes of neutrophils and lymphocytes from patients with bacterial and viral infections.Inflammation 9:53–65.Google Scholar
  22. 22.
    Niwa, Y., Y. Miyachi, T. Sakane, T. Kanoh, andS. Taniguchi. 1988. Methyltransferase and phospholipase A2 activity in the cell membrane of neutrophils and lymphocytes from patients with Behçet's disease, systemic lupus erythematosus, and rheumatoid arthritis.Clin. Chim. Ada 174:1–14.Google Scholar
  23. 23.
    Niwa, Y., andS. Taniguchi. 1986. Phospholipid base exchange in human leukocyte membranes: Quantitation and correlation with other phospholipid biosynthetic pathways.Arch. Biochem. Biophys. 250:345–357.Google Scholar
  24. 24.
    Hirata, F., andJ. Axelrod. 1980. Phospholipid methylation and biological signal transmission.Science 209:1082–1090.Google Scholar
  25. 25.
    Ishizaka, T., F. Hirata, andK. Ishizaka. 1980. Stimulation of phospholipid methylation, Ca2+ influx, and histamine release by bridging of IgG receptors on rat cells.Proc. Natl. Acad. Sci. U.S.A. 77:1903–1906.Google Scholar
  26. 26.
    Nishizuka, Y. 1989. Studies and prospectives of the protein kinase C family for cellular regulation.Cancer 63:1892–1903.Google Scholar
  27. 27.
    Berridge, M. J., andR. F. Irvine. 1984. Inositol triphosphate, a novel second messenger in cellular signal transduction.Nature 312:315–321.Google Scholar
  28. 28.
    Nishizuka, Y. 1986. Studies and perspectives of protein kinase C.Science 233:305–312.Google Scholar
  29. 29.
    Kaibuchi, K., Y. Takai, andM. Sawamura. 1983. Synergistic functions of protein phosphorylation and calcium mobilization in platelet activation.J. Biol. Chem. 258:6701–6704.Google Scholar
  30. 30.
    Niwa, Y., T. Sakane, M. Shingu, I. Yanagida, J. Komura, andY. Miyachi. 1985. Neutrophil-generated active oxygens in linear IgA bullous dermatosis.Arch. Dermatol. 121:73–78.Google Scholar
  31. 31.
    Skosey, J. L., E. Damgaard, D. C. Chow, andL. B. Sorensen. 1974. Modification of zymosan-induced release of lysosomal enzymes from polymorphonuclear leukocytes by cytochalasin B.J. Cell. Biol. 62:625–634.Google Scholar
  32. 32.
    Johnson, A. R., andG. Erdos. 1977. Metabolism of vasoactive peptides by human endothelial cells in culture.J. Clin. Invest. 59:684–695.Google Scholar
  33. 33.
    Nelson, R. D., P. G. Quie, andR. L. Simmons. 1977. Chemotaxis under agarose. A new and simple method for measuring chemotaxis and spontaneous migration of human polymorphonuclear leukocytes and monocytes.J. Immunol. 115:1650–1656.Google Scholar
  34. 34.
    Stossel, T. P. 1973. Evalaation of opsonic and leukocyte function with a spectrophotometric test in patients with infection and with phagocytic disorders.Blood 42:121–130.Google Scholar
  35. 35.
    Bligh, E. G., andW. J. Dyer. 1959. A rapid method of total lipid extraction and purification.Can. J. Biochem. Physiol. 37:911–917.Google Scholar
  36. 36.
    Johnston, R. B., Jr., andJ. E. Lehmeyer. 1976. Elaboration of toxic oxygen by-products by neutrophils and a model of immune complex disease.J. Clin. Invest. 57:836–841.Google Scholar
  37. 37.
    Massey, V. 1959. The microestimation of succinate and the extinction coefficient of cytochrome c.Biochim. Biophys. Acta 34:255–256.Google Scholar
  38. 38.
    Root, R. K., andJ. A. Metcalf. 1972. H2O2 release from human granulocytes during phagocytosis.J. Clin. Invest. 60:1266–1279.Google Scholar
  39. 39.
    Klebanoff, S. J., andH. Rosen. 1978. Ethylene formation by polymorphonuclear leukocytes.J. Exp. Med. 148:490–505.Google Scholar
  40. 40.
    Niwa, Y., T. Sakane, andY. Miyachi. 1984. Dissociation of the inhibitory effect of dapsone on the generation of oxygen intermediates—in comparison with that of colchicine and various scavengers.Biochem. Pharmacol. 33:2355–2360.Google Scholar
  41. 41.
    Johnson, P. C., J. A. Ware, P. B. Cliveden, M. Smith, A. M. Dvorak, andE. W. Salzman. 1985. Measurement of ionized calcium in blood platelets with the photoprotein aequorin: Comparison with quin 2.J. Biol. Chem. 260:2069–2076.Google Scholar
  42. 42.
    Grynkiewicz, G., M. Poenie, andR. Y. Tsien. 1985. A new generation of Ca2+ indicators with greatly improved fluorescence properties.J. Biol. Chem. 260:3440–3450.Google Scholar
  43. 43.
    Ozaki, Y., andS. Kume. 1988. Functional responses of aequorin-loaded human neutrophils. Comparison with fura-2-loaded cells.Biochim. Biophys. Acta 972:113–119.Google Scholar
  44. 44.
    Park, B. H., S. M. Firkimg, andE. M. Smithwick. 1968. Infection and nitroblue tetrazolium reduction by neutrophils. A diagnostic acid.Lancet 2:532–534.Google Scholar
  45. 45.
    Baehner, R. L. 1979. The growth and development of our understanding of chronic granulomatous disease.In The Phagocytic Cell in Host Resistence. J. A. Bellanti and D. H. Dayton, editors. Raven Press, New York. 173–178.Google Scholar
  46. 46.
    Kohashi, O., Y. Kohashi, andN. Shigematsu. 1985. In vivo and in vitro effects of adjuvants on generation of active oxygen metabolites of leukocytes-in relation to leukocyte subpopulation.Jpn. Soc. Immunol. 15:144.Google Scholar

Copyright information

© Plenum Publishing Corporation 1991

Authors and Affiliations

  • Yukie Niwa
    • 1
  • Hirohiko Akamatsu
    • 1
  1. 1.Department of DermatologyKansai Medical UniversityMoriguchiJapan

Personalised recommendations