Sepsis-induced acute kidney injury (AKI) is responsible for 70-80% mortality in intensive care patients due to elevated levels of endotoxin, Lipopolysaccharide (LPS) caused by gram-negative infections. Ferulic acid (FA), a phenolic phytochemical is known for its renal protection on various induced models of nephrotoxicity. However, the curative effect of FA in LPS-induced AKI is not well studied. This study aimed to investigate the effect of FA on LPS-induced AKI in mice model and to understand the protective mechanisms involved, to provide evidence for FA in the treatment of AKI. Balb/c mice were treated with FA at 50 mg/kg and 100 mg/kg dosages after LPS stimulation (10 mg/kg). At the end of the intervention, we determined the concentrations of serum creatinine and blood urea nitrogen, inflammatory cytokines and histopathological changes in animals. Also, the relative protein expression level of TLR4 mediated NF-κB signaling pathway were studied in kidney tissues. FA treated animals showed upregulation of antioxidant defenses and suppression of inflammatory events by inhibiting TLR-4 mediated NFκB activation. However, LPS alone administered group, resulted in rapid renal damage with increased levels of blood urea nitrogen and modest increase in creatinine; decreased antioxidant defenses and release of inflammatory cytokines. The histopathological analysis also revealed the protective action of the FA against sepsis induced fibrosis and renal damage. Our findings demonstrated that FA exhibits marked protective effects on LPS-induced AKI in mice suggesting its chemopotential role for treating AKI in humans.
Keywords: Acute kidney injury (AKI); Antioxidants; Ferulic acid (FA); Lipopolysaccharide (LPS); NFκB pathway; Sepsis.
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