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N-acetylcysteine lacks universal inhibitory activity against influenza A viruses.

Garigliany MM, Desmecht DJ - J Negat Results Biomed (2011)

Bottom Line: N-acetylcysteine (NAC) has been recently proposed as an adjuvant therapeutic drug for influenza pneumonia in humans.In this study, we show that NAC is unable to alter the course of a fatal influenza pneumonia caused by inoculation of a murinized swine H1N1 influenza virus.Therefore, susceptibility of influenza viruses to NAC appears to be strain-dependent, suggesting that it cannot be considered as a universal treatment for influenza pneumonia.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pathology, Faculty of Veterinary Medicine, University of Liège, Belgium. mmgarigliany@ulg.ac.be

ABSTRACT
N-acetylcysteine (NAC) has been recently proposed as an adjuvant therapeutic drug for influenza pneumonia in humans. This proposal is based on its ability to restrict influenza virus replication in vitro and to attenuate the severity of the disease in mouse models. Although available studies were made with different viruses (human and avian), published information related to the anti-influenza spectrum of NAC is scarce. In this study, we show that NAC is unable to alter the course of a fatal influenza pneumonia caused by inoculation of a murinized swine H1N1 influenza virus. NAC was indeed able to inhibit the swine virus in vitro but far less than reported for other strains. Therefore, susceptibility of influenza viruses to NAC appears to be strain-dependent, suggesting that it cannot be considered as a universal treatment for influenza pneumonia.

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Effect of mock and N-acetylcysteine oral treatment on body weight course after inoculation of 10 DL50 of H1N1 virus in mice. Means ± SD (n = 10).
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Figure 2: Effect of mock and N-acetylcysteine oral treatment on body weight course after inoculation of 10 DL50 of H1N1 virus in mice. Means ± SD (n = 10).

Mentions: All mice became obviously sick from day 5 pi onward, with lethargy, ruffled coat and respiratory distress. Percent survival and mean survival time (Figure 1) were not different between NAC and control groups (p > 0.05, Kaplan-Meier analysis). Moreover, course and amplitude of BW loss (Figure 2) were similar (p > 0.05, ANOVA). Altogether, the results therefore show that a daily dose of 100 mg/kg NAC did not confer protection against influenza disease in our experimental conditions. The dose of NAC given here (100 mg/kg) is typically that used for high dose NAC treatment of human severe influenza pneumonia in recent clinical trials [6]. Some of the former studies that have enlighted the protective efficacy of NAC in mouse models have used an oral dose of 1000 mg/kg, which suggests that the dose given here is not sufficient. However, 100 mg/kg NAC is already considered as a high dose in humans, and 1000 mg/kg is obviously unrealistic for humans because too close to the LD50 [2,3,8,9]. The fact that a dose of NAC close to that used here drastically diminished mouse lung damages in a diesel-enhanced influenza pneumonia [10] whereas it did not work here rather suggests that the use of different virus strains results in different susceptibilities to NAC in vivo.


N-acetylcysteine lacks universal inhibitory activity against influenza A viruses.

Garigliany MM, Desmecht DJ - J Negat Results Biomed (2011)

Effect of mock and N-acetylcysteine oral treatment on body weight course after inoculation of 10 DL50 of H1N1 virus in mice. Means ± SD (n = 10).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3104374&req=5

Figure 2: Effect of mock and N-acetylcysteine oral treatment on body weight course after inoculation of 10 DL50 of H1N1 virus in mice. Means ± SD (n = 10).
Mentions: All mice became obviously sick from day 5 pi onward, with lethargy, ruffled coat and respiratory distress. Percent survival and mean survival time (Figure 1) were not different between NAC and control groups (p > 0.05, Kaplan-Meier analysis). Moreover, course and amplitude of BW loss (Figure 2) were similar (p > 0.05, ANOVA). Altogether, the results therefore show that a daily dose of 100 mg/kg NAC did not confer protection against influenza disease in our experimental conditions. The dose of NAC given here (100 mg/kg) is typically that used for high dose NAC treatment of human severe influenza pneumonia in recent clinical trials [6]. Some of the former studies that have enlighted the protective efficacy of NAC in mouse models have used an oral dose of 1000 mg/kg, which suggests that the dose given here is not sufficient. However, 100 mg/kg NAC is already considered as a high dose in humans, and 1000 mg/kg is obviously unrealistic for humans because too close to the LD50 [2,3,8,9]. The fact that a dose of NAC close to that used here drastically diminished mouse lung damages in a diesel-enhanced influenza pneumonia [10] whereas it did not work here rather suggests that the use of different virus strains results in different susceptibilities to NAC in vivo.

Bottom Line: N-acetylcysteine (NAC) has been recently proposed as an adjuvant therapeutic drug for influenza pneumonia in humans.In this study, we show that NAC is unable to alter the course of a fatal influenza pneumonia caused by inoculation of a murinized swine H1N1 influenza virus.Therefore, susceptibility of influenza viruses to NAC appears to be strain-dependent, suggesting that it cannot be considered as a universal treatment for influenza pneumonia.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pathology, Faculty of Veterinary Medicine, University of Liège, Belgium. mmgarigliany@ulg.ac.be

ABSTRACT
N-acetylcysteine (NAC) has been recently proposed as an adjuvant therapeutic drug for influenza pneumonia in humans. This proposal is based on its ability to restrict influenza virus replication in vitro and to attenuate the severity of the disease in mouse models. Although available studies were made with different viruses (human and avian), published information related to the anti-influenza spectrum of NAC is scarce. In this study, we show that NAC is unable to alter the course of a fatal influenza pneumonia caused by inoculation of a murinized swine H1N1 influenza virus. NAC was indeed able to inhibit the swine virus in vitro but far less than reported for other strains. Therefore, susceptibility of influenza viruses to NAC appears to be strain-dependent, suggesting that it cannot be considered as a universal treatment for influenza pneumonia.

Show MeSH
Related in: MedlinePlus