Protocatechuic acid ameliorates lipopolysaccharide‐induced kidney damage in mice via downregulation of TLR‐4‐mediated IKBKB/NF‐κB and MAPK/Erk signaling pathways

Abstract Acute kidney injury (AKI) is a very critical cause of death in the whole world. Lipopolysaccharide (LPS) induces kidney damage by activating various deleterious inflammatory and oxidative pathways. Protocatechuic acid, a natural phenolic compound, has shown to exert beneficial effects against oxidative and inflammatory responses. The study aimed to clarify the nephroprotective activity of protocatechuic acid in LPS‐induced acute kidney damage in mice. Forty male Swiss mice were allocated in four groups as follows: normal control group; LPS (250 μg/kg, ip)‐induced kidney injury group; LPS‐injected mice treated with protocatechuic acid (15 mg/kg, po), and LPS‐injected mice treated with protocatechuic acid (30 mg/kg, po). Significant toll‐like receptor 4 (TLR‐4)‐mediated activation of IKBKB/NF‐κB and MAPK/Erk/COX‐2 inflammatory pathways has been observed in kidneys of mice treated with LPS. Oxidative stress was revealed by inhibition of total antioxidant capacity, catalase, nuclear factor erythroid 2‐related factor 2 (Nrf2), and NAD(P)H quinone oxidoreductase (NQO1) enzyme along with increased nitric oxide level. In parallel, focal inflammatory effects were shown in between the tubules and glomeruli as well as in the perivascular dilated blood vessels at the cortex affecting the normal morphology of the kidney tissues of LPS‐treated mice. However, treatment with protocatechuic acid reduced LPS‐induced changes in the aforementioned parameters and restored normal histological features of the affected tissues. In conclusion, our study uncovered that protocatechuic acid has nephroprotective effects in mice with AKI through opposing different inflammatory and oxidative cascades.