Targeting NLRP3 inflammasome via acetylsalicylic acid: Role in suppressing hepatic dysfunction and insulin resistance induced by atorvastatin in naïve versus alcoholic liver in rats

Abstract Background NLRP3 inflammasome is described in many pathological conditions and is also involved in drug induced liver injury. Aim of the work To investigate the role of NLRP3 inflammasome in liver injury induced by chronic alcohol and/or atorvastatin ingestion. Materials and methods Sixty male Wistar rats were used. They were divided into 5 groups: (I) control naive (II) Alcoholic: given ethanol 8 g/kg/day, p.o (III) Atorvastatin: given atorvastatin 10 mg/kg/day, p.o. (IV) Alcoholic + atorvastatin (V) Acetylsalicylic acid (ASA): given ASA 10 mg/kg/day, p.o together with alcohol and atorvastatin. Isolated perfused liver, biochemical and histological studies were done. Results Atorvastatin and alcohol induced liver inflammation with increasing the expression of NLRP3, IL-1β and caspase-8 immune-reaction. Atorvastatin and alcohol decreased the reduced form of glutathione in hepatic tissues and induced insulin resistance. ASA administration alleviated the hepatotoxic effects of alcohol and atorvastatin to a significant extent. Conclusions Acetylsalicylic acid alleviated the hepatotoxic effects of alcohol and atorvastatin through decreasing the production of NLRP3 inflammasome in rats' liver.