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

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.

Canagliflozin Ameliorates NLRP3 Inflammasome-Mediated Inflammation Through Inhibiting NF-κB Signaling and Upregulating Bif-1

“…CAN significantly attenuated lipotoxicity and inflammation in cardiomyocytes ( Sun et al, 2021 ). CAN significantly reduced IL-1β levels in the plasma and lung tissues of LPS-treated NIH mice and THP-1 cells stimulated by LPS ( Xu et al, 2018 ; Niu et al, 2021 ). However, the exact molecular mechanisms remain to be elucidated.…”

“…Several studies and clinical trials have shown that CAN reduces the risk of cardiovascular events ( Neal et al, 2017 ; Kosiborod et al, 2018 ; Mahaffey et al, 2018 ; Sun et al, 2021 ). We previously found that CAN effectively alleviated the pathological changes in lung inflammation in LPS-treated NIH mice ( Xu et al, 2018 ; Niu et al, 2021 ) and reduced the level of IL-1β in lung tissue and plasma ( Niu et al, 2021 ). However, the specific mechanism is still unclear.…”

Anti-Hyperglycemic Agents in the Adjuvant Treatment of Sepsis: Improving Intestinal Barrier Function

“… Attenuating cytokine storm and reducing inflammation. [ 151 ] Blood vessel Mice; LPS Canagliflozin protected against sepsis capillary leak syndrome. Acting on the α1AMPK-dependent pathway.…”

Huashibaidu formula attenuates sepsis-induced acute lung injury via suppressing cytokine storm: Implications for treatment of COVID-19

“…The ATP competitive kinase inhibitor baricitinib reduces the viral entry into target cells and controls the cytokine storm, thus preventing damage to the lungs and possibly other organs in severe COVID-19 patients ( Zhang et al, 2020 ). The sodium glucose cotransporter 2 (SGLT2) inhibitor canagliflozin improved acute lung injuries induced by LPS-treated mouse sepsis by inhibiting cytokine storms ( Niu et al, 2021 ). These pharmaceutical studies provide a scientific reference for the treatment of a series of diseases related to cytokine storms.…”