TY - JOUR
T1 - In vitro lymphotoxicity and selective T cell immunotoxicity of high doses of acyclovir and its derivatives in mice
AU - Poluektova, L.
AU - Krzystyniak, K.
AU - Desjardins, R.
AU - Flipo, D.
AU - Fournier, M.
N1 - Funding Information:
Acknowledgements-L.P. received postdoctoral fellowship from Toxen, Universite du Quebec a Montreal, and from Latvian Sores Foundation. Present address: Laboratory of Immunogenetics and Immunology, Latvian Medical Academy, Riga, Latvia. The authors thank Dr. R. Zhuk and Dr. M. Madre from Latvian Institute of Organic Synthesis for providing ACV analogues. This work was supported by Toxen, Universite du Quebec a Montreal, and Canadian Network of Toxicology Centres.
PY - 1996/6
Y1 - 1996/6
N2 - The antiviral drug acyclovir [9-(2-hydroxyethoxymethyl)guanine (ACV)], its 7-isomer (7-ACV) and its two derivatives: N2-acetyl ACV (ac-ACV) and N2,O-diacetyl ACV (diac-ACV) were examined for their potential in vitro lymphotoxicity and in vivo immunotoxicity in mice. In vitro lymphotoxicity of ACV and its acetylated derivatives was low, whereas the 7-ACV isomer enhanced the in vitro cell proliferation in PHA-stimulated cultures. Addition of 2'-deoxyguanosine (dGuo) did not exhibit any inhibitory potential of ACV. However, reduction in the absolute number of CD3+, CD8+, and CD25+ cells, but not Ig+ cells, was noted at high concentrations of ACV and its derivatives, suggesting a selective T cell cytotoxicity. Similarly, the in vivo exposure revealed selective T cell immunotoxicity of ACV and its derivatives since the reduced number of Thy 1.2+ and CD8+ cells was not accompanied with any marked changes in the Ig+ population. The CD4+/CD8+ ratio was affected both in vitro and in vivo by high concentrations of ACV.
AB - The antiviral drug acyclovir [9-(2-hydroxyethoxymethyl)guanine (ACV)], its 7-isomer (7-ACV) and its two derivatives: N2-acetyl ACV (ac-ACV) and N2,O-diacetyl ACV (diac-ACV) were examined for their potential in vitro lymphotoxicity and in vivo immunotoxicity in mice. In vitro lymphotoxicity of ACV and its acetylated derivatives was low, whereas the 7-ACV isomer enhanced the in vitro cell proliferation in PHA-stimulated cultures. Addition of 2'-deoxyguanosine (dGuo) did not exhibit any inhibitory potential of ACV. However, reduction in the absolute number of CD3+, CD8+, and CD25+ cells, but not Ig+ cells, was noted at high concentrations of ACV and its derivatives, suggesting a selective T cell cytotoxicity. Similarly, the in vivo exposure revealed selective T cell immunotoxicity of ACV and its derivatives since the reduced number of Thy 1.2+ and CD8+ cells was not accompanied with any marked changes in the Ig+ population. The CD4+/CD8+ ratio was affected both in vitro and in vivo by high concentrations of ACV.
KW - Acyclovir
KW - Cytometric assay
KW - Immunopharmacolog
KW - Immunotoxicity
KW - In vitro lymphotoxicity
KW - Lymphocyte subsets
KW - Mouse lymphocyte
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U2 - 10.1016/S0192-0561(96)00017-3
DO - 10.1016/S0192-0561(96)00017-3
M3 - Article
C2 - 9024946
AN - SCOPUS:0030158085
SN - 1567-5769
VL - 18
SP - 429
EP - 438
JO - International Immunopharmacology
JF - International Immunopharmacology
IS - 6-7
ER -