nifuroxazide and Sepsis

Acute lung injury (ALI) and the subsequent multi-system organ failure is a serious health problem with devastating impacts on the health care systems. Indeed, the world has been facing an un-preceded situation in the past couple of months following COVID-19 infestation and the associated high-mortality rates mainly attributed to sepsis and the associated multiple organ failures of particular concern; acute respiratory distress syndrome post lung injury. The current study provides evidence on the ameliorative impact of nifuroxazide, and FDA approved antidiarrheal drug in attenuation of lipopolysaccharide (LPS)-induced ALI and myocarditis when administrated either in prophylactic or curative regimens. Nifuroxazide administration was associated with a significant improvement in lung and heart histopathological characteristics and architecture with retraction of LPS-induced inflammatory-infiltration. This was associated with retraction in serum biomarkers of cellular injury of which; LDH, CK-MB, and ALP. Nifuroxazide administration was associated with a significant improvement in both lung and heart oxidative status. Such positive outcomes were underlined by a significant inhibitory effect of nifuroxazide on lung and heart contents of toll-like receptor (4) (TLR4)/the inflammasome NALPR3/interleukin- 1β (IL-1β). In conclusion: Nifuroxazide attenuates LPS-induced ALI and myocardial injury via interruption of TLR4/NALPR3/IL-1β signaling. Thus it can offer a potential approach for attenuation of sepsis in critically ill patients.

Topics: Acute Lung Injury; Animals; Coronavirus Infections; COVID-19; Disease Models, Animal; Hydroxybenzoates; Interleukin-1beta; Lipopolysaccharides; Male; Multiple Organ Failure; Myocarditis; Nitrofurans; NLR Family, Pyrin Domain-Containing 3 Protein; Pandemics; Pneumonia, Viral; Rats; Rats, Sprague-Dawley; Sepsis; Signal Transduction; Toll-Like Receptor 4