Intragastric and atomized administration of canagliflozin inhibit inflammatory cytokine storm in lipopolysaccharide-treated sepsis in mice: A potential COVID-19 treatment

https://doi.org/10.1016/j.intimp.2021.107773Get rights and content

Highlights

  • Drugs to attenuate cytokine storm in COVID-19 are unavailable.

  • Canagliflozin attenuated inflammatory cytokine storm in LPS-treated mice..

  • Atomized administration of Canagliflozin also exhibited anti-inflammatory effects.

Abstract

To date, drugs to attenuate cytokine storm in severe cases of Corona Virus Disease 2019 (COVID-19) are not available. In this study, we investigated the effects of intragastric and atomized administration of canagliflozin (CAN) on cytokine storm in lung tissues of lipopolysaccharides (LPS)-induced mice. Results showed that intragastric administration of CAN significantly and widely inhibited the production of inflammatory cytokines in lung tissues of LPS-induced sepsis mice. Simultaneously, intragastric administration of CAN significantly improved inflammatory pathological changes of lung tissues. Atomized administration of CAN also exhibited similar effects in LPS-induced sepsis mice. Furthermore, CAN significantly inhibited hypoxia inducible factor 1α (HIF-1α) and phosphofructokinase-2/fructose-2,6-bisphosphatase 3 (PFKFB3) protein levels in LPS-treated lung tissues. These results indicated that CAN might attenuate cytokine storm and reduce the inflammatory symptoms in critical cases in COVID-19. Its action mechanism might involve the regulation of HIF-1α and glycolysis in vivo. However, further studies about clinical application and mechanism analysis should be validated in the future.

Keywords

Canagliflozin
COVID-19
Cytokine storm
Inflammation

Abbreviations

CAN
Canagliflozin
CMC
sodium carboxymethylcellulose
COVID-19
Corona Virus Disease 2019
DXM
dexamethasone
GM-CSF
granulocyte- macrophage colony stimulating factor
HIF-1α
hypoxia inducible factor 1α
IFN-γ
interferon γ
interleukin
IL
KC
keratinocyte-derived chemokine
LIX
LPS-induced CXC Chemokine
LPS
lipopolysaccharides
MIP-2
Macrophage inflammatory protein 2-α
MCP-1
monocyte chemotactic protein 1
PFKFB3
phosphofructokinase-2/fructose-2,6-bisphosphatase 3
SGLT2
sodium glucose transporter 2
TNF-α
tumor necrosis factor α

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1

Equal contribution.

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