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Targeting NLRP3 inflammasome via acetylsalicylic acid: Role in suppressing hepatic dysfunction and insulin resistance induced by atorvastatin in naïve versus alcoholic liver in rats.
Biomedicine & Pharmacotherapy 2018 November
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 naïve (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.
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 naïve (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.
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