Effect of 6-azacytidine on the course of experimental adenoviral infection in newborn Syrian hamsters.
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.
Zarubalev
V V
VV
Influenza Research Institute, Saint Petersburg, Russian Federation, Kiev, Ukraine. zarubaev@influenza.spb.ru
Slita
A V
AV
Sukhinin
V P
VP
Nosach
L N
LN
Dyachenko
N S
NS
Povnitsa
O Y
OY
Zhovnovataya
V L
VL
Alexeeva
I V
IV
Palchikovskaya
L I
LI
D000257:Adenoviridae Infections / Q000188:drug therapy* / Q000473:pathology; D000260:Adenoviruses, Human / Q000187:drug effects; D000818:Animals; D000831:Animals, Newborn; D000998:Antiviral Agents / Q000627:therapeutic use*; D001374:Azacitidine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D006224:Cricetinae; D004195:Disease Models, Animal; D008647:Mesocricetus; D013154:Spleen / Q000187:drug effects / Q000473:pathology
D000998:Antiviral Agents; D001374:Azacitidine; C040881:6-azacytidine