Abstract
Septic acute kidney injury (AKI) is an important medical problem worldwide, but current treatments are limited. During sepsis, lipopolysaccharide (LPS) activates various signaling pathways involved in multiorgan failure. Carnosic acid is a natural phenolic diterpene and has multiple bioactivities, such as anti-tumor, anti-inflammatory, and anti-oxidative effects. However, the effect of carnosic acid on septic AKI has not been explored. Therefore, this study aimed to determine whether carnosic acid has a therapeutic effect on LPS-induced kidney injury. Administration of carnosic acid after LPS injection ameliorated histological abnormalities and renal dysfunction. Cytokine production, immune cell infiltration, and nuclear factor-κB activation after LPS injection were also alleviated by carnosic acid. The compound suppressed oxidative stress with the modulation of pro-oxidant and antioxidant enzymes. Tubular cell apoptosis and caspase-3 activation were also inhibited by carnosic acid. These data suggest that carnosic acid ameliorates LPS-induced AKI via inhibition of inflammation, oxidative stress, and apoptosis and could serve as a useful treatment agent for septic AKI.
Highlights
Sepsis is a clinical syndrome of systemic inflammatory responses to infection and can lead to multiorgan failure [1]
To determine whether carnosic acid exerts a therapeutic action on endotoxin-induced kidney injury, we first examined the effect of carnosic acid on histological abnormalities in LPS-injected mice
We showed that carnosic acid ameliorates tubular injury in endotoxin-injected mice, as evidenced by improvement in tubular injury score, reduction in the loss of Lotus tetragonolobus lectin (LTL)-stained brush border, and downregulation of neutrophil-gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1)
Summary
Sepsis is a clinical syndrome of systemic inflammatory responses to infection and can lead to multiorgan failure [1]. Acute kidney injury (AKI) is the most serious and common complication of sepsis [2]. Current management of septic AKI consists of early administration of antibiotics, use of appropriate vasopressor agents, and fluid resuscitation [3]. The current treatment is reactive and nonspecific and its effectiveness is not sufficient [3]. The development of new, effective strategies or medications for septic AKI is of great clinical importance. LPS is released into the systemic circulation and binds to Toll-like receptors (TLRs), activating several signaling pathways involved in multiorgan failure [3,4,5]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
