Synergistic combination of N-acetylcysteine and ribavirin to protect from lethal influenza viral infection in a mouse model.
Oxidative stress is implicated in the pathogenesis of pulmonary damage during viral infections. In a previous study we observed a significant improvement of survival of influenza-infected mice with NAC, 1g/kg divided in two daily administrations, for 8 days including a pretreatment on day 1 before infection. In order to test NAC in a more realistic model, we studied the effect of combined treatment with NAC and the antiviral drug, ribavirin. Since in the present work we wanted to test a possible synergistic effect by combination of NAC and ribavirin, we used a different NAC's treatment regimen (1 g/kg, once a day for 4 days) that, alone, did not significantly protect mice from death. Mice (12 per group) infected intranasally with a lethal dose of influenza A virus APR/8. NAC was given as a single daily dose of 1000 mg/kg starting from 4 h after infection and until day 4 after infection, in association with ribavirin (100 mg/kg, i.p.). End-point evaluation was 14-day survival. With this schedule survival in infected mice was 17%, it was not significantly changed by NAC (25%). Survival increased to 58% with ribavirin and to 92% (n=12) with a combined treatment with ribavirin and NAC. This suggest that antioxidant therapy can increase survival by either improving the defenses against virus or by protecting from the pathogenesis of lung inflammation.
Ghezzi
P
P
Mario Negri Institute, Milan, Italy. ghezzi@marionegri.it
Ungheri
D
D
D000111:Acetylcysteine / Q000627:therapeutic use*; D000818:Animals; D004195:Disease Models, Animal; D004357:Drug Synergism; D009980:Influenza A virus / Q000187:drug effects / Q000276:immunology; D008297:Male; D051379:Mice; D009976:Orthomyxoviridae Infections / Q000188:drug therapy / Q000401:mortality* / Q000517:prevention & control*; D012254:Ribavirin / Q000627:therapeutic use*; D015996:Survival Rate
D012254:Ribavirin; D000111:Acetylcysteine