Mechanistically, our data indicated that FICZ significantly upregulates NAD( P)H quinone oxidoreductase 1 and heme oxygenase 1 via aryl hydrocarbon receptor (AhR) and nuclear factor erythroid 2–related factor 2 (Nrf2) in the kidneys to lessen inflammation and improve septic acute kidney injury. ![]() Furthermore, we found that FICZ dampens both renal and systemic inflammation in our sepsis model. Our results show that FICZ reduced LPS-induced acute injury in kidneys from LPS-injected mice. ![]() Thereafter, gene expression of kidney injury and pro-inflammatory markers, circulating cytokines and chemokines, and kidney morphology were assessed. To test this, male C57Bl/6N mice were injected with FICZ (0.2 mg/kg) or vehicle 1 h prior to an injection of either lipopolysaccharides (LPS) (10 mg/kg), to induce sepsis, or phosphate-buffered saline for 24 h. As several studies have suggested that 6-formylindolo(3,2-b)carbazole (FICZ) is beneficial for treating various inflammatory diseases, we aimed to examine the potential protective effect of FICZ on the acute endotoxin-induced sepsis model of kidney injury. Thus, dampening inflammation-induced renal injury may limit severe consequences of sepsis. Although sepsis is accompanied by multiple organ injuries, acute renal injury is a significant contributor to sepsis morbidity and mortality. Patients with sepsis are at a high risk of morbidity and mortality due to multiple organ injuries caused by pathological inflammation.
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