Antiviral efficacy and toxicity of ribavirin in murine acquired immunodeficiency syndrome model.

Abstract

The antiretroviral efficacy and hematotoxicity of ribavirin, a guanosine analogue, have been evaluated in mice infected with the LP-BM5 virus pool [murine acquired immunodeficiency syndrome (MAIDS) model]. Doses ranging from 6.25 to 200 mg/kg/day were injected intraperitoneally twice a day for 6 weeks to infected mice. Drug treatment induced a significant protection against splenomegaly and lymphadenopathy at doses > or = 25 mg/kg. Moreover, doses starting at 50 mg/kg protected against hypergammaglobulinemia, minimized the loss of spleen CD8+ T cells, and reconstituted the capacity of splenocytes to proliferate in response to concanavalin A. The spleen and cervical lymph node architectures were protected, and a reduction in the emergence of germinal centers was observed at 50 mg/kg ribavirin. Hematotoxicity appeared at doses > or = 50 mg/kg ribavirin, and severe anemia was predominant only at doses of 100 and 200 mg/kg. This study shows that ribavirin protects mice against the effects resulting from retrovirus infection at doses of > or = 50 mg/kg in a MAIDS model and induces severe hematotoxicity at doses > or = 100 mg/kg.

• Authors: P Harvie, R F Omar, N Dusserre, A Désormeaux, P Gourde, M Tremblay, D Beauchamp, M G Bergeron
• Journal: Journal of acquired immune deficiency syndromes and human retrovirology : official publication of the International Retrovirology Association (J Acquir Immune Defic Syndr Hum Retrovirol) Vol. 12 Issue 5 Pg. 451-61 (Aug 15 1996) ISSN: 1077-9450 [Print] United States
• PMID: 8757421 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antiviral Agents
• Immunoglobulin M
• Concanavalin A
• Ribavirin

Topics

• Acquired Immunodeficiency Syndrome (drug therapy)
• Animals
• Antiviral Agents (administration & dosage, therapeutic use, toxicity)
• Blood Cell Count
• CD4-CD8 Ratio
• Cell Division (drug effects)
• Concanavalin A (pharmacology)
• Disease Models, Animal
• Female
• Immunoglobulin M (blood)
• Leukemia Virus, Murine
• Lymph Nodes (pathology)
• Mice
• Mice, Inbred C57BL
• Murine Acquired Immunodeficiency Syndrome (drug therapy, immunology, pathology)
• Organ Size
• Ribavirin (administration & dosage, therapeutic use, toxicity)
• Spleen (cytology, pathology)