Mol Biol Rep. 2026 Jun 5;53(1):893. doi: 10.1007/s11033-026-12056-7.
ABSTRACT
BACKGROUND: Lipopolysaccharide (LPS)-induced sepsis is one of the leading causes of acute kidney injury (AKI). Gallic acid (GAL), a natural polyphenolic compound, exhibits potent antioxidant, anti-inflammatory, and cytoprotective properties. This study aimed to investigate the renoprotective effects of GAL.
METHODS: Thirty-two adult male Wistar rats were randomly divided into four groups (n = 8): Control, LPS (5 mg/kg, i.p.), LPS + GAL (100 mg/kg i.p. administered immediately before LPS), representing a preventive treatment design and GAL-alone. Renal tissues were examined histologically using hematoxylin-eosin staining and toll-like receptor 4(TLR4), nuclear factor kappa B(NF-κB), and interleukin-1 beta (IL-1β) immunoexpression by immunohistochemical staining. mRNA expression levels of sirtuin 1(SIRT1), adenosine monophosphate-activated protein kinase(AMPK), forkhead box O3(FOXO3), phosphoinositide 3-kinase (PI3K), protein kinase B(AKT1), glutathione peroxidase 4(GPX4), aquaporin 4 (AQP4), glycogen synthase kinase-3 beta(GSK3β) were assessed. Serum creatinine (CRE) and urea levels were analyzed to determine renal functional status.
RESULTS: LPS administration caused marked renal injury, characterized by severe hyperemia, hemorrhage, tubular necrosis, and increased TLR4, NF-κB, and IL-1β expression. GAL treatment attenuated these changes, with a significant reduction only in hyperemia scores, while decreases in hemorrhage, neutrophil infiltration, and necrosis remained nonsignificant. GAL administration was associated with reversal of the LPS-related decrease in PI3K, AKT1, AMPK, FOXO3, SIRT1, GPX4 and AQP4 mRNA expression, along with reduced GSK3β mRNA expression. Serum CRE levels improved with GAL, whereas the urea reduction was not statistically significant.
CONCLUSION: GAL showed a renoprotective effect in this preventive model of LPS-induced AKI and was associated with reduced inflammatory marker expression together with favorable changes in PI3K/AKT1/FOXO3/SIRT1-related mRNA profiles. These findings suggest that GAL may have prophylactic against early endotoxin-associated renal injury.
PMID:42247065 | DOI:10.1007/s11033-026-12056-7
