New therapeutic target in inflammation: Emerging role of dapagliflozin in overcoming lipopolysaccharide-mediated lung injury

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By E. E. Abd El-Fattah, S. Saber, Simona Cavalu et al.

Effect of dapagliflozin (5 and 10 mg/kg) on the histological features of LPS-induced lung injury. Lung specimens of the Control or DPGZ animals exhibited no
histological alterations of normal bronchioles (B), normal alveoli (A), normal airspaces (AS), and normal alveolar wall thickening (arrowhead). However, LPSexposed
rats exhibited massive inflammatory-cell infiltration of neutrophils, macrophages and lymphocytes (arrows), alveolar wall thickening (arrowheads),
fibrinous exudates (star) and the highest of both the inflammation score and the lung lesion distribution score. In contrast, DPGZ at both the lowest dose and
particularly the highest dose resulted in a marked improvement in lung histological features of lower degree of inflammatory-cell infiltration (arrows) and alveolar
wall thickening (arrowheads) and a significant decline in both the inflammation score and the lung lesion distribution score compared to LPS-exposed rats. Copyright E. E. Abd El-Fattah, S. Saber, Simona Cavalu et al.
Effect of DPGZ (5 and 10 mg/kg) on the level of (A) SOD, (B) CAT, (C) GSH, (D) NOx, and (E) MDA in rats with LPS-induced ALI. SOD: superoxide dismutase, CAT: catalase, GSH: reduced glutathione, NOx: nitric oxide, MDA: malondialdehyde, DPGZ: dapagliflozin, LPS:
lipopolysaccharides. Copyright E. E. Abd El-Fattah, S. Saber, Simona Cavalu et al.

Effect of dapagliflozin treatment on inflammatory markers: MPO activity as well as MCP-1, IL-1β, IL-18, and TNF-α levels. Copyright E. E. Abd El-Fattah, S. Saber, Simona Cavalu et al.
Effect of DPGZ (5 and 10 mg/kg) on p-AMPK/t-AMPK ratio in rats with LPS-induced ALI.
p-AMPK: phosphorylated adenosine monophosphate phosphate kinase, t-AMPK: total adenosine monophosphate phosphate kinase, DPGZ: dapagliflozin, LPS: lipopolysaccharides. Copyright E. E. Abd El-Fattah, S. Saber, Simona Cavalu et al.
Effect of dapagliflozin treatment on NLRP3 levels, NLRP3 gene expression, and caspase-1 activity. Copyright E. E. Abd El-Fattah, S. Saber, Simona Cavalu et al.
Effect of dapagliflozin treatment on NF-kB P65 binding activity and NFĸB p65 (pSer536) levels in rats with LPS-induced ALI. NF-kB: nuclear factor kappa B, DPGZ: dapagliflozin, LPS: lipopolysaccharides. Copyright E. E. Abd El-Fattah, S. Saber, Simona Cavalu et al.

Acute lung injury (ALI) is one the most common causes of morbidity and mortality in critically ill patients. In this study, we examined for first time the role of dapagliflozin (DPGZ) in lipopolysaccharide (LPS)-induced ALI in rats and determined the underlying molecular mechanisms by evaluating the effects of DPGZ on adenosine monophosphate kinase (AMPK), nuclear transcription factor kappa B, nucleotide-binding and oligomerization domain-like receptor 3 inflammasome activation. Copyright E. E. Abd El-Fattah, S. Saber, Simona Cavalu et al.

Full text available at : https://www.sciencedirect.com/science/article/pii/S0753332222000166#fig0005

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