medigraphic.com

2000, Número 4

Siguiente >>

Vet Mex 2000; 31 (4)


Estudio comparativo de los efectos antivirales de agentes antioxidantes: N-acetilcisteína y ácido ascórbico e inmunosupresores: Ciclosporina A y tacrolimus en células crónicamente infectadas con el virus de la inmunodeficiencia felina

Mórtola E, Endo Y, Risso M, Gimeno E

Idioma: Español/Inglés
Referencias bibliográficas: 42
Paginas: 271-277
Archivo PDF: 67.26 Kb.


RESUMEN

To examine the antiviral action of antioxidants and immunosuppressive drugs on feline immunodeficiency virus (VIF), the effects of noncytotoxic concentrations of two antioxidants, N-acetylcysteine (NAC) and ascorbic acid (AA) and two immunosuppressive agents, cyclosporin A (CsA) and Tracrolimus (also known as FK506) on the inhibition of the replication of the virus and of apoptosis in a feline fibroblastic cell line chronically infected with VIF were studied and compared. Long-term treatment of the infected cells with NAC and AA induced a significant inhibition of viral replication and apoptosis after addition of tumor necrosis factor alfa (TNF-a). Both CsA and FK506 significantly suppressed virus production and apoptosis activity by about the same magnitude as the equivalent dose of NAC and AA. The twenty two day experiment showed that continuous presence of the agents was necessary for VIF inhibition, because the removal of the drugs resulted in the resumption of virus replication. These in vitro results suggest that the antiviral effects of the antioxidants and immunosuppressive agents tested in this study have potential implications for the design of therapeutic strategies in VIF infection.


REFERENCIAS (EN ESTE ARTÍCULO)

  1. Pedersen NC, Yamamoto JK, Ishida T, Hansen H. Feline immunodeficiency infection. Vet Immunol Immunopathol 1989;21:111-129.

  2. Yamamoto JK, Hansen H. Epidemiologic and clinical aspects of feline immunodeficiency virus (VIF) infection in cats from the continental United States and Canada and possible mode of transmission. J Am Vet Med Assoc 1989;194:213-220.

  3. Dow SW, Poss ML, Hoover EA. Feline immunodeficiency virus: a neurotropic lentivirus. J Acq Immun Def Synd 1990;3:658-668.

  4. Walker NI, Harmon BV, Gobe GC, Kerr JF. Patterns of cell death. Methods Arch Exp Pathol 1988;13:18-25.

  5. Hoffmann-Fezer G, Thum J, Ackley CD. Decline in CD4+ cell numbers in cats with naturally acquired feline immunodeficiency virus infection. J Virol 1992;66:1484-1488.

  6. Pedersen NC, Ho EW, Brown ML, Yamamoto JK. Isolation of a T lymphotropic virus from domestic cats with an immunodeficiency like syndrome. Science 1987;235:790-793.

  7. Bishop SA, Gruffydd-Jones TJ, Harbour DA, Stokes CR. Programmed cell death (apoptosis) as a mechanism of cell death in peripheral blood mononuclear cells from cats infected with feline immunodeficiency virus (VIF). Clin Exp Immunol 1993;93:65-71.

  8. Ohno K, Nakano T, Matsumoto Y, Watari T, Goitsuka R, Nakayama H, et al. Apoptosis induced by tumor necrosis factor in cells chronically infected with feline immunodeficiency virus. J Virol 1993;67:2429-2433.

  9. Ohno K, Okamoto Y, Miyazawa T, Mikami T, Watari T, Goitsuka R, et al. Induction of apoptosis in a T-lymphoblastoid cell line infected with feline immunodeficiency virus. Arch Virol 1994;135:153-158.

  10. Momoi Y, Takuya M, Nishimura Y, Endo Y, Ohno K, Watari T, et al. Detection of apoptosis induced in peripheral blood lymphocytes from cats infected with feline immunodeficiency virus. Arch Virol 1996;141:1651-1659.

  11. Roederer M, Staal FJ, Raju PA, Ela SW, Herzenberg LA, Herzenberg LA. Cytokine-stimulated VIH replication is inhibited by N-acetylcysteine. Proc Natl Acad Sci USA 1990;87:4884-4888.

  12. Eck HP, Gmunder H, Hartmann M, Petzoldt D, Daniel V, Droge W. Low concentration of acid-soluble thiol (cysteine) in the blood plasma of VIH-1-infected patients. Biol Chem Hoppe-Seyler 1989;370:101-108.

  13. Greenspan HC, Aruoma OI. Oxidative stress and apoptosis in VIH infection: a role for plant-derived metabolites with synergistic antioxidants activity (review). Immunol Today 1994;15:209-213.

  14. McGowan AJ, Fernandes RS, Samali A, Cotter TG. Anti-oxidants and apoptosis (review). Biochem Soc Trans 1996;24:229-233.

  15. Mathieu J, Chancerelle Y, Herodin F, Multon E, Drouet M, Mestries JC, et al. Oxidative stress and apoptosis (review). Ann Pharm Fr 1996;54:193-201.

  16. Boman G, Backer U, Larsson S, Melander B, Wahlander L. Oral acetilcysteine reduces exacerbation rate in chronic bronchitis: report of a trial organized by the Swedish Society for Pulmonary Diseases. Eur J Respir Dis 1983;64:405-415.

  17. British Thoracic Society Research Committee. Oral N-acetylcysteine and exacerbation rates in patients with chronic bronchitis and severe airways obstruction. Thorax 1985;40:832-835.

  18. Moldeus P, Cotgreave IA, Bergren M. Lung protection by a thiol-containing antioxidant: N-acetylcysteine. Respiration 1986;50:31-42.

  19. Klenner FR. Observations on the dose and administration of ascorbic acid when employed beyond the range of a vitamin in human pathology. J Appl Nutr 1971;23:61-87.

  20. Cathcart RF. Vitamin C: titrating to bowel tolerance, anascorbemia, and acute induced scurvy. Med Hypotheses 1981;5:54-58.

  21. 21 . Harakeh S, Jariwalla RJ, Pauling L. Suppression of human immunodeficiency virus replication by ascorbate in chronically and acutely infected cells. Proc Natl Acad Sci USA 1990;87:7245-7249.

  22. Schreiber SL. Immunophilin-sensitive protein phosphatase action in cell signaling pathways. Cell 1992;70:365-368.

  23. Schreiber SL, Crabtree GR. The mechanism of action of cyclosporin A and FK506. Immunol Today 1992;13:136-142.

  24. Sigal NH, Dumont FJ. Cyclosporin A, FK-506, and rapamycin: pharmacologic probes of lymphocyte signal transduction. Ann Rev Immunol 1992;10:519-560.

  25. Mórtola E, Okuda M, Ohno K, Watari T, Tsujimoto H, Hasegawa A. Inhibition of apoptosis and virus replication in feline immunodeficiency virus-infected cells by N-acetilcysteine and ascorbic acid. J Vet Med Sci 1998;60:1181-1185.

  26. Mórtola E, Endo Y, Ohno K, Watari T, Tsujimoto H, Hasegawa A The use of two immunosuppressive drugs: CsA and FK 506 to inhibit viral replication and apoptosis in cells infected with feline immunodeficiency virus. Vet Res Comm 1998;22:553-563.

  27. Crandell RA, Fabricant CG, Nelson-Rees WA. Development, characterization, and viral susceptibility of a feline (Felis catus) renal cell line (CRFK). In vitro 1973;9:176-185.

  28. Miyazawa T, Furuya T, Itagaki S, Tohya Y, Nakano K, Takahashi E, Mikami T. Preliminary comparisons of the biological properties of two strains of feline immunodeficiency virus (VIF) isolated in Japan with VIF Petaluma strain isolated in the United States. Arch Virol 1989;108:59-68.

  29. Bissell MJ, Hatie C, Farson DA, Schwarz RI, Soo WJ. Ascorbic acid inhibits replication and infectivity of avian RNA tumor virus. Proc Natl Acad Sci USA 1980;77:2711-2715.

  30. De-Vries N, De-Flora S. N-acetyl-l-cysteine. J Cell Biochem Suppl 1993;17F:270-277.

  31. Roederer M, Ela SW, Frank JT, Staal FJ, Herzenberg L. N-acetylcysteine: a new approach to anti-VIH therapy. AIDS Res Hum Retrovir 1992;8:209-217.

  32. Poli G, Bressler P, Kinter A, Duh E, Timmer WC, Rabson A, et al. Interleukin 6 induces human immunodeficiency virus expression in infected monocytic cells alone and in synergy with tumor necrosis factor-alpha by transacriptional and post-transcriptional mechanisms. J Exp Med 1990;172:151-158.

  33. Luban J, Bossolt KL, Franke E, Kalpana GV, Goff SP. Human immunodeficiency virus type 1 Gag protein binds to cyclophilin A and B. Cell 1993;73:1067-1078.

  34. Franke EK, Yuan HE, Luban J. Specific incorporation of cyclophilin A into VIH-1 virions. Nature (London) 1994;372:359-362.

  35. Thali M, Bukovsky A, Kondo E. Functional association of a cyclophilin A with VIH-1 virions. Nature 1994;372:363-365.

  36. Braaten D, Franke EK, Luban J. Cyclophilin A is required for the replication of group M human immunodeficiency virus type 1 (VIH-1) and simian immunodeficiency virus SIVcpz GAB but not group O VIH-1 or other primate immunodeficiency viruses. J Virol 1996;70:4220-4227.

  37. Elder JH, Schnolzer M, Hasselkus-Light CS, Henson M, Lerner DA, Phillips TR, et al. Identification of proteolytic processing sites within the Gag and Pol polyproteins of feline immunodeficiency virus. J Virol 1993;67:1869-1876.

  38. Franke EK, Luban J. Inhibition of VIH-1 replication by cyclosporine A or related compounds correlates with the ability to disrupt the Gag-Cyclophilin A interaction. Virology 1996;222:279-282.

  39. Bartz SR, Hohenwalter E, Hu M, Rich DH, Malkovsky M. Inhibition of human immunodeficiency virus replication by non-immunosuppressive analogs of cyclosporin A. Proc Natl Acad Sci USA 1995;92:5381-5385.

  40. Karpas A, Lowdell M, Jacobson SK, Hill F. Inhibition of human immunodeficiency virus and growth of infected T cells by the immunosuppressive drugs cyclosporin A and FK506. Proc Natl Acad Sci USA 1992;89:8351-8355.

  41. Steinkasserrer A, Harrison H, Billich A, Hammerschmid F, Werner G, Wolff B, et al. Mode of action of SDZ NIM 811, a non-immunosuppressive cyclosporin A analog with activity against human immunodeficiency virus type 1 (VIH-1): interference with early and late events in VIH-1 replication. J Virol 1995;69:814-824.

  42. Bishop SA, Williams NA, Gruffydd-Jones TJ, Harbour DA, Stokes CR. Impaired T-cell priming in cats infected with feline immunodeficiency virus (VIF). AIDS 1993;6:287-293.




2020     |     www.medigraphic.com