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.