2.4 Other diuretics as inhaled anti-inflammatory agents
Loop diuretics: In addition to furosemide, other
diuretics with structural similarities to furosemide’s anthranilate
molecular core are reported to exhibit analogous anti-inflammatory
properties. Hung and co-workers (2018) showed that bumetanide reduced
the production of pro-inflammatory cytokines upon direct pulmonary
administration, lowered levels of TNFα in mice and showed
anti-inflammatory activity in RAW264.7 cells stimulated by
pro-inflammatory lipopolysaccharides (LPS). In another study
investigating lung injury induced by ischemia-reperfusion, bumetanide
showed a similar effect. Compared to a control group, mice given
bumetanide during the reperfusion period were reported to have a lower
level of TNFα production. Although bumetanide failed to inhibit sodium
metabisulfite(MBS)-induced bronchoconstriction in asthmatic subjects,
another loop diuretic, piretanide, is reported to have protective
effects against MBS-mediated bronchoconstriction. The protective effect,
however, did not correlate with the diuretic properties of piretanide.
These findings are supported by work from Bianco et al. in which
piretanide was as effective as furosemide in preventing
bronchoconstriction induced by ultrasonically nebulized distilled water.
Yet another loop diuretic that exhibits effects on cytokine production
is azosemide (Hampel et al. ; 2018).
Osmotic diuretics: Although not structurally related to
furosemide (See Figure 2), other diuretics have also been suggested to
have inflammatory properties targeting pulmonary disorders. Mannitol is
an osmotic diuretic sometimes used to reduce increased intracranial
pressure. Inhaled dry powder mannitol has been evaluated as a
therapeutic for cystic fibrosis and bronchiectasis. de Nijs et
al. (2011) have shown that the therapeutic effect of inhaled mannitol
against chronic obstructive pulmonary disease is reflected by favourable
alterations in IL-8 and eosinophil biomarkers.