Sinapic Acid Attenuates LPS‐Induced Acute Kidney Injury in Rats: Changes in Autophagy‐Related, Apoptotic, Inflammatory, and Oxidative Stress Markers

ABSTRACT

Lipopolysaccharide (LPS)‐induced acute kidney injury (AKI) is associated with high morbidity and mortality. The molecular mechanisms underlying sepsis‐associated renal injury remain incompletely understood. Sinapic acid (SA), a bioactive phenolic compound, exhibits antioxidant, anti‐inflammatory, and cytoprotective properties, but its nephroprotective role in LPS‐induced AKI has not been clarified. We evaluated the protective effects of SA in an LPS‐induced AKI rat model and examined its associations with autophagy‐related, apoptotic, inflammatory, and oxidative stress markers. AKI was induced by a single intraperitoneal injection of LPS (5 mg/kg) following 7 days of oral SA pretreatment (40 mg/kg/day). LPS administration caused marked renal tubular injury and significantly increased serum BUN, CREA, and UA levels. SA pretreatment significantly attenuated these alterations. Moreover, LPS increased renal BECN1 immunoreactivity and circulating SQSTM1/p62 levels, indicating alterations in autophagy‐related markers, together with increased renal TNF‐α and Caspase‐3 immunoreactivity. SA pretreatment significantly attenuated the LPS‐induced increases in these markers. LPS also increased renal MDA levels and serum total oxidant status. SA pretreatment significantly reduced renal MDA without significantly altering SOD, GPx, or total antioxidant status, indicating attenuation of lipid peroxidation rather than a generalized enhancement of antioxidant defenses. Furthermore, SA attenuated the LPS‐induced reductions in serum albumin and total protein and the increase in LDH. Collectively, these findings suggest that SA pretreatment attenuates LPS‐induced AKI and that this protective effect is accompanied by changes in autophagy‐related markers, reduced renal TNF‐α and Caspase‐3 immunoreactivity, and decreased renal lipid peroxidation.