Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
권호 표지
DOI QR코드

DOI QR Code

Immunotoxicological Investigation of 1-furan-2-yl-3-pyridin-2-yl-propenone in Female BALB/c Mice

  • Published : 2009.10.31
Download PDF
⟨ Previous Next ⟩

Abstract

1-Furan-2-yl-3-pyridin-2-yl-propenone (FPP-3) has recently been synthesized and characterized to have an anti-inflammatory activity through the inhibition of the production of nitric oxide and tumor necrosis factor-$\alpha$. In the present study, adverse effects of FPP-3 on immune functions were determined in female BALB/c mice. When mice were administered orally with FPP-3 at 125, 250 or 500 mg/kg for 7 consecutive days, FPP-3 suppressed the number of antibody-forming cells and reduced thymus weight at 500 mg/kg. In addition, FPP-3 administered mice exhibited reduced splenic cellularity and numbers of splenocyte subsets, such as $CD3^+$ cells, $CD3^+CD4^+$ cells, $CD3^+CD8^+$ cells and macrophages. IL-4 mRNA expression was significantly suppressed by FPP-3 treatment. Moreover, the number of $CD4^+IL-4^+$ cells was reduced following the treatment of mice with 500 mg/kg of FPP-3. These results suggested that FPP-3 at 500 mg/kg might be immunotoxic, and that FPP-3-induced immunotoxicity might be mediated, at least in part, through the inhibition of cytokine production, such as IL-4.

Keywords

References

  1. Davila, D. R., Davis, D. P., Campbell, K., Cambier, J. C., Zigmond, L. A. and Burchiel, S. W. (1995). Role of alterations in Ca2＋-associated signaling pathways in the immunotoxicity of polycyclic aromatic hydrocarbons. J. Toxicol. Environ. Health 45, 101-126. https://doi.org/10.1080/15287399509531985
  2. Dean, J. H., Ward, E. C., Murray, M. J., Lauer, L. D. and House, R. V. (1985). Mechanisms of dimethylbenzanthraceneinduced immunotoxicity. Clin. Physiol. Biochem. 3, 98-110.
  3. Fearon, D. T. and Locksley, R. M. (1996). The instructive role of innate immunity in the acquired immune response. Science 272, 50-53. https://doi.org/10.1126/science.272.5258.50
  4. Ginsberg, G. L., Atherholt, T. B. and Butler, G. H. (1989). Benzo[a]pyrene-induced immunotoxicity: comparison to DNA adduct formation in vivo, in cultured splenocytes, and in microsomal systems. J. Toxicol. Environ. Health 28, 205-220. https://doi.org/10.1080/15287398909531341
  5. Jahng, Y., Zhao, L. X., Moon, Y. S., Basnet, A., Kim, E. K., Chang, H. W., Ju, H. K., Jeong, T. C. and Lee, E. S. (2004). Simple aromatic compounds containing propenone moiety show considerable dual COX/5-LOX inhibitory activities. Bioorg. Med. Chem. Lett. 14, 2559-2562. https://doi.org/10.1016/j.bmcl.2004.02.099
  6. Jeon, T. W., Jin, C. H., Lee, S. K., Lee, D. W., Hyun, S. H., Kim, G. H., Jun, I. H., Lee, B. M., Yum, Y. N., Kim, J. K., Kim, O. H. and Jeong, T. C. (2005). In vivo and in vitro immunosuppressive effects of benzo[k]fluoranthene in female BALB/c mice. J. Toxicol. Environ. Health A. 68, 2033-2050. https://doi.org/10.1080/15287390491009147
  7. Jeon, T. W., Kim, C. H., Lee, S. K., Shin, S., Choi, J. H., Kang, W., Kim, S. H., Kang, M. J., Lee, E. S. and Jeong, T. C. (2009). Hepatotoxic effects of 1-furan-2-yl-3-pyridin-2-ylpropenone, an anti-inflammatory agent, in male ICR mice. Biomol. Ther. 17, 318-324. https://doi.org/10.4062/biomolther.2009.17.3.318
  8. Kaminski, N. E., Barnes, D., Jordan, S. D. and Holsapple, M. P. (1990). The role of metabolism in carbon tetrachloridemediated immunosuppression. In vivo studies. Toxicol. Appl. Pharmacol. 102, 9-20. https://doi.org/10.1016/0041-008X(90)90079-A
  9. Kremer, J., Gleichmann, E. and Esser, C. (1994). Thymic stroma exposed to arylhydrocarbon receptor-binding xenobiotics fails to support proliferation of early thymocytes but induces differentiation. J. Immunol. 153, 2778-2786.
  10. Kurt-Jones, E. A., Hamberg, S., Ohara, J., Paul, W. E. and Abbas, A. K. (1987). Heterogeneity of helper/inducer T lymphocytes. I. Lymphokine production and lymphokine responsiveness. J. Exp. Med. 166, 1774-1787. https://doi.org/10.1084/jem.166.6.1774
  11. Lee, E. S., Ju, H. K., Moon, T. C., Lee, E., Jahng, Y., Lee, S. H., Son, J. K., Baek, S. H. and Chang, H.W. (2004). Inhibition of nitric oxide and tumor necrosis factor-$\alpha$ (TNF-$\alpha$) production by propenone compound through blockade of nuclear factor (NF)-${\kappa}B$ activation in cultured murine macrophages. Biol. Pharm. Bull. 27, 617-620. https://doi.org/10.1248/bpb.27.617
  12. Luster, M. I., Munson, A. E., Thomas, P. T., Holsapple, M. P., Fenters, J. D., White, K. L. Jr., Lauer, L. D., Germolec, D. R., Rosenthal, G. J. and Dean, J. H. (1988). Development of a testing battery to assess chemical-induced immunotoxicity: National Toxicology Program's guidelines for immunotoxicity evaluation in mice. Fundam. Appl. Toxicol. 10, 2-19. https://doi.org/10.1016/0272-0590(88)90247-3
  13. Luster, M. I., Portier, C., Pait, D. G., Rosenthal, G. J., Germolec, D. R., Corsini, E., Blaylock, B. L., Pollock, P., Kouchi, Y., Craig, W., White, K. L. Jr., Munson, A. E. and Comment, C. E. (1993). Risk assessment in immunotoxicology. II. Relationships between immune and host resistance tests. Fundam. Appl. Toxicol. 21, 71-82. https://doi.org/10.1006/faat.1993.1074
  14. Luster, M. I., Portier, C., Pait, D. G., White, K. L. Jr., Gennings, C., Munson, A. E. and Rosenthal, G. J. (1992). Risk assessment in immunotoxicology. I. Sensitivity and predictability of immune tests. Fundam. Appl. Toxicol. 18, 200-210. https://doi.org/10.1016/0272-0590(92)90047-L
  15. Mosmann, T. R., Cherwinski, H., Bond, M. W., Giedlin, M. A. and Coffman, R. L. (1986). Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. J. Immunol. 136, 2348-2357.
  16. Mosmann, T. R. and Sad, S. (1996). The expanding universe of T-cell subsets: Th1, Th2 and more. Immunol. Today 17, 138-146. https://doi.org/10.1016/0167-5699(96)80606-2
  17. Mullen, A. C., High, F. A., Hutchins, A. S., Lee, H. W., Villarino, A. V., Livingston, D. M., Kung, A. L., Cereb, N., Yao, T. P., Yang, S. Y. and Reiner, S. L. (2001). Role of T-bet in commitment of TH1 cells before IL-12-dependent selection. Science 292, 1907-1910. https://doi.org/10.1126/science.1059835
  18. Myers, M. J., Blanton, R. H. and Bick, P. H. (1988). Inhibition of IL-2 responsiveness following exposure to benzo(a)pyren is due to alterations in accessory cell function. Int. J. Immunopharmacol. 10, 177-186. https://doi.org/10.1016/0192-0561(88)90093-8
  19. Okey, A. B., Dube, A. W. and Vella, L. M. (1984). Binding of benzo(a)pyren and dibenz(a,h)anthracene to the Ah receptor in mouse and rat hepatic cytosols. Cancer Res. 44, 1426-1432.
  20. Pallardy, M., Mishal, Z., Lebrec, H. and Bohuon, C. (1992). Immune modification due to chemical interference with transmembrane signaling: application to polycyclic aromatic hydrocarbons. Int. J. Immunopharmacol. 14, 377-382. https://doi.org/10.1016/0192-0561(92)90167-J
  21. Seder, R. A., Paul, W. E., Davis, M. M. and de St Groth, B. F. (1992). The presence of interleukin 4 during in vitro priming determines the lymphokine-producing potential of $CD4^+$ T cells from T cell receptor transgenic mice. J. Exp. Med. 176, 1091-1098. https://doi.org/10.1084/jem.176.4.1091
  22. Shi, L., Nishioka, W. K., Th'ng, J., Bradbury, E. M., Litchfield, D. W. and Greenberg, A. H. (1994). Premature p34cdc2 activation required for apoptosis. Science 263, 1143-1145. https://doi.org/10.1126/science.8108732
  23. Swain, S. L., Bradley, L. M., Croft, M., Tonkonogy, S., Atkins, G., Weinberg, A. D., Duncan, D. D., Hedrick, S. M., Dutton, R. W. and Huston, G. (1991). Helper T-cell subsets: phenotype, function and the role of lymphokines in regulating their development. Immunol. Rev. 123, 115-144. https://doi.org/10.1111/j.1600-065X.1991.tb00608.x
  24. Whitehurst, C. E. and Geppert, T. D. (1996). MEK1 and the extracellular signal-regulated kinases are required for the stimulation of IL-2 gene transcription in T cells. J. Immunol. 156, 1020-1029.