Effect of 6-azacytidine on the course of experimental adenoviral infection in newborn Syrian hamsters

J Chemother. 2007 Feb;19(1):44-51. doi: 10.1179/joc.2007.19.1.44.

Abstract

Adenoviral infection is a serious human pathology leading to respiratory, gastrointestinal and ocular disorders and epidemic outbreaks, especially in children's groups. Here we present the results from an investigation of anti- adenoviral effect of 6-azacytidine (6-AC) both in vitro and in vivo. The selectivity index of 6-AC for adenovirus type 5 in HEp-2 cells was 374, the 50% effective concentration was 0.5 mg/ml. For in vivo investigations we developed a model of disseminated adenoviral infection in newborn Syrian hamsters. The infectious virus was recovered from the liver, kidney, lungs and heart. Application of 6-AC led to a reduced period of the virus presence (7 days in the liver and 4 days in the kidney and heart) and lowered virus titers on day 3 post-inoculation (p.i.) (liver - 2.7 and 4.1, heart - 0 and 3.2, kidney - 0 and 2.4 log(10 )CPD(50)/mg tissue weight, in the presence and absence of 6-AC, respectively). Application of 6-AC to newborn Syrian hamsters led to partial destruction of their splenocytes. The results obtained suggest that 6-AC or 6-ACbased drugs with lower toxicity or applied topically may be suitable for therapy and prevention of adenoviral infection in humans.

MeSH terms

  • Adenoviridae Infections / drug therapy*
  • Adenoviridae Infections / pathology
  • Adenoviruses, Human / drug effects
  • Animals
  • Animals, Newborn
  • Antiviral Agents / therapeutic use*
  • Azacitidine / analogs & derivatives*
  • Azacitidine / pharmacology
  • Azacitidine / therapeutic use
  • Cricetinae
  • Disease Models, Animal
  • Mesocricetus
  • Spleen / drug effects
  • Spleen / pathology

Substances

  • Antiviral Agents
  • Azacitidine
  • 6-azacytidine