Chlorogenic acid alleviates acute kidney injury in septic mice by inhibiting NLRP3 inflammasomes and the caspase-1 canonical pyroptosis pathway

Abstract

To investigate the role of caspase-1-medicated canonical pyroptosis pathway in chlorogenic acid (CGA) treatment of acute kidney injury (AKI) in mice. Twenty-four C57Bl/6J mice were randomized into sham-operated group, cecal ligation and puncture (CLP) group, CLP+dexamethasone group (CLP+DXM group), and CLP+CGA group (n=6) and subjected to either sham operation (laparotomy only) or CLP. After modeling the mice received intravenous infusion of 10 mg/kg normal saline (in sham and CLP groups), 1 μg/kg dexamethasone or 15 mg/kg of chlorogenic acid for 6 h delivered using an intravenous pump. Eight hours after the infusion, renal morphology and histology, renal cell apoptosis, and the renal function parameters such as urea nitrogen (BUN), creatinine (Scr), and kidney injury molecule 1 (KIM-1) were compared among the 4 groups; the 7-day survival rates of the mice were recorded, and the expressions of NLRP3 inflammasomes and key proteins of the caspase-1 pathway in the renal tissue were detected. CGA treatment significantly improved the 7-day survival rate, reduced renal pathologies of the septic mice (P < 0.05), and lowered the levels of BUN, Scr, KIM-1, NLRP3 inflammasome and expressions of key proteins of the caspase-1 pathway. CGA alleviates AKI in mice with CLP-induced sepsis by inhibiting NLRP3 inflammasomes and the caspase-1 signaling pathway.