Glutathione
and Influenza
Inhibition
of influenza infection by glutathione.
Cai J, Chen Y, Seth S, Furukawa S, Compans RW, Jones DP. [Free
Radic Biol Med. 2003 Apr 1;34(7):928-36.]
Infection by RNA virus induces oxidative stress in host cells. Accumulating
evidence suggests that cellular redox status plays an important role
in regulating viral replication and infectivity. In this study, experiments
were performed to determine whether the thiol antioxidant glutathione
(GSH) blocked influenza viral infection in cultures of Madin-Darby
canine kidney cells or human small airway epithelial cells. Protection
against production of active virus particles was observed at a low
(0.05-0.1) multiplicity of infection (MOI). GSH inhibited expression
of viral matrix protein and inhibited virally induced caspase activation
and Fas upregulation. In BALB/c mice, inclusion of GSH in the drinking
water decreased viral titer in both lung and trachea homogenates 4
d after intranasal inoculation with a mouse-adapted influenza strain
A/X-31. Together, the data suggest that the thiol antioxidant
GSH has an anti-influenza activity in vitro and in vivo. Oxidative
stress or other conditions that deplete GSH in the epithelium of the
oral, nasal, and upper airway may, therefore, enhance susceptibility
to influenza infection.
Attenuation
of influenza-like symptomatology and improvement of cell-mediated
immunity with long-term N-acetylcysteine treatment.
De Flora S, Grassi C, Carati L. [Eur Respir J. 1997 Jul;10(7):1535-41.]
N-acetylcysteine (NAC), an analogue and precursor of reduced glutathione,
has been in clinical use for more than 30 yrs as a mucolytic drug.
It has also been proposed for and/or used in the therapy and/or prevention
of several respiratory diseases and of diseases involving an oxidative
stress, in general. The objective of the present study was to evaluate
the effect of long-term treatment with NAC on influenza and influenza-like
episodes. A total of 262 subjects of both sexes (78% > or = 65
yrs, and 62% suffering from nonrespiratory chronic degenerative diseases)
were enrolled in a randomized, double-blind trial involving 20 Italian
Centres. They were randomized to receive either placebo or NAC tablets
(600 mg) twice daily for 6 months. Patients suffering from chronic
respiratory diseases were not eligible, to avoid possible confounding
by an effect of NAC on respiratory symptoms. NAC treatment was well
tolerated and resulted in a significant decrease in the frequency
of influenza-like episodes, severity, and length of time confined
to bed. Both local and systemic symptoms were sharply and significantly
reduced in the NAC group. Frequency of seroconversion towards A/H1N1
Singapore 6/86 influenza virus was similar in the two groups, but
only 25% of virus-infected subjects under NAC treatment developed
a symptomatic form, versus 79% in the placebo group. Evaluation of
cell-mediated immunity showed a progressive, significant shift from
anergy to normoergy following NAC treatment. Administration of N-acetylcysteine
during the winter, thus, appears to provide a significant attenuation
of influenza and influenza-like episodes, especially in elderly high-risk
individuals. N-acetylcysteine did not prevent A/H1N1 virus influenza
infection but significantly reduced the incidence of clinically apparent
disease.
Publication Types:
Clinical Trial
Multicenter Study
Randomized Controlled Trial
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