2.3 Anti-viral properties of furosemide
Besides its anti-inflammatory properties and positive effects in
dyspnoea, furosemide has also been shown to exhibit anti-viral
properties. Voss et al. (1996) concluded that furosemide
inhibited the
Na+/K+/2Cl-cotransporter and thereby blocked the cytopathic effects of alterations
in intracellular cation concentration induced by the human
immunodeficiency virus (HIV), a single-stranded, positive-sense,
enveloped RNA virus member of the genus Lentivirus , part of the
family Retroviridae . In cells infected with a cytopathic strain
of HIV-1, the activity of the
Na+/K+/2Cl-cotransporter was significantly increased, leading to a higher
Na+ and K+ concentrations and
thereby to an increased cell volume. This pathological swelling can then
lead to membrane disruption and ultimately cell death. Inhibition of the
Na+/K+/2Cl-cotransporter by furosemide, however, was able to reduce this
pathological process, prolonging the survival of cells by 2-4 weeks.
Ulug et al. (1989) studied the influence of cation gradients in
the release of Sindbis virus, a positive-sense, single-stranded
RNA virus, from infected cells. The cell volume of Sindbis virus
infected cells is reduced and the activity of the
Na+/K+ ATPase is decreased,
presumably to maintain a higher, intracellular concentration of
monovalent cations. Especially in low salt media, but also, with reduced
extent, in isotonic media, the treatment of infected cells with
furosemide inhibited the release of Sindbis virus from these
cells through the inhibition of the
Na+/K+/2Cl-cotransporter. In another study by Hartley et al. (2006), the
effect of furosemide-induced inhibition of the
Na+/K+/2Cl-cotransporter in DNA and RNA viruses was explored. According to these
authors, DNA viruses are dependent upon K+ for
replication, thus stopping K+ influx by inhibition of
the Na+/K+/2Cl-cotransporter would have broad-spectrum anti-viral effects. While
reduced replication was indeed observed for DNA viruses, the replication
of the RNA virus was not inhibited. These multiple studies all conclude
that the pathologic alteration of intracellular cation concentrations
mediated by viral action can be blocked by furosemide through inhibition
of the Na+/K+/2Cl-cotransporter.
Finally, it is important to note that furosemide’s anti-viral activities
do not require systemic administration of the drug. Indeed, topical and
locally administered furosemide gel has demonstrated efficacy against
warts caused by the human papillomavirus.