Targeting NLRP3 inflammasome via acetylsalicylic acid: Role in suppressing hepatic dysfunction and insulin resistance induced by atorvastatin in naïve versus alcoholic liver in rats - 20/09/18
, Dalia Alaa El-Din Aly El-Waseef b , Enas S. Nabih c , Doaa I. Mohamed a Bienvenido a EM-consulte, la referencia de los profesionales de la salud.
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Graphical abstract |
Highlights |
• | NLRP3 inflammasome is involved in drug induced liver injury. |
• | Hepatotoxic effect of atorvastatin is exaggerated by chronic alcohol ingestion. |
• | Alcohol/atorvastatin increased hepatic expression of NLRP3 and IL-1β. |
• | Low dose ASA alleviated the hepatotoxic effect of alcohol/atorvastatin. |
• | Low dose ASA acts through NLRP3 inflammasome/caspase-8/ IL-1β pathway. |
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 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.
El texto completo de este artículo está disponible en PDF.Abbreviations : AFL, ALD, ALK, ALT, ASA, AST, Bcl2, BSP, COX-I, GSH, GSSG, HFD, HOMA-IR, IL-1β, KCs, MDB, NLRP3, OS, PCR, rER, ROS, RT, sER, UDP-glucuronosyltransferase
Keywords : Acetylsalicylic acid, Alcohol, Atorvastatin, NLRP3, Inflammasome
Esquema
Vol 107
P. 665-674 - novembre 2018 Regresar al número
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Bienvenido a EM-consulte, la referencia de los profesionales de la salud.
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Bienvenido a EM-consulte, la referencia de los profesionales de la salud.
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