Efficacy of chlorogenic acid against ethylene glycol-induced renal stone model: The role of NFKB-RUNX2-AP1-OSTERIX signaling pathway

Abstract

Background and objectiveRenal tissue injuries by free radicals are an essential reason in pathogenesis of urinary tract stones. Ethylene glycol is one of the toxic agents which can causes to the increases in biosynthesis of reactive oxygen species and oxidative stress condition. Natural antioxidants have been reported to protective efficacy against renal stones formation. Accordingly, the aim of the current experiment was to identify the renal protective effect of chlorogenic acid as a well-prominent antioxidant on ethylene glycol-induced renal stone model targeting the NFKB-RUNX2-AP1-OSTERIX signaling pathway. Materials and methodsRenal stones model were established by ethylene glycol (Percent: 0.75) within the daily drinking water for rats. Treatment groups received cystone (750 mg/kg) and chlorogenic acid (100, 200, and 400 mg/kg, day: 15th to 28th, gavage). After 4 weeks, the renal function parameters (calcium, uric acid, creatinine, total protein, oxalate, and citrate) in plasma, urine, and renal tissue were measured. Moreover, oxidative stress factors and gene expression of NFKB, RUNX2, AP1, and OSTERIX were also evaluated. ResultsThe results showed improved renal function in chlorogenic acid-treated groups. The total proteins and creatinine excretion were decreased. Also the gene expression of oxidative stress pathway (NFKB-RUNX2-AP1-OSTERIX) were decreased which caused to increases of antioxidant enzymes. Conclusionsthe antioxidant activity increases by chlorogenic acid treatment may have a critical role in prevention of calcium oxalate formation via inhibition of the NFKB-RUNX2-AP1-OSTERIX signaling pathway.