Acute atorvastatin is hepatoprotective against ischaemia-reperfusion injury in mice by modulating eNOS and microparticle formation

Liver International : Official Journal of the International Association for the Study of the Liver
Hussam AjamiehNarci C Teoh

Abstract

Steatosis accentuates the severity of hepatic ischaemia-reperfusion injury (IRI); 'statins' (HMG-CoA reductase inhibitors) protect the heart and brain against post-ischaemic injury. We tested whether short-term administration of atorvastatin protects fatty livers in obese mice against IRI. Mice with dietary or genetic simple steatosis (SS) or non-alcoholic steatohepatitis (NASH) were subjected to 60 min partial hepatic ischaemia/24 h reperfusion. Atorvastatin was injected intravenously (5 mg/kg) 1 h before IRI. Liver injury, Toll-like receptor-4 (TLR4), cytokines/chemokines, iNOS/eNOS expression, eNOS activity and thromboxane B2 (TXB2) production were determined. Ischaemia-reperfusion injury was exaggerated by two- to five-fold in SS and NASH compared with lean liver. Atorvastatin pretreatment conferred 70-90% hepatic protection in all animals. Atorvastatin increased post-ischaemic eNOS mRNA/protein and strikingly enhanced eNOS activity (by phospho-eNOS). It also attenuated microparticle (MP) production, NF-κB activation, significantly dampened post-ischaemic thromboxane B2 production, induction of TNF-α, IL-6, MIP-1a, MCP-1, GM-CSF and vascular cell adhesion molecule-1 (VCAM), with a resultant reduction on macrophage and polym...Continue Reading

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Citations

Mar 18, 2016·International Journal of Molecular Sciences·Linda A BanSusan V McLennan
Jun 29, 2017·Expert Review of Gastroenterology & Hepatology·Tetsu Yamamoto, Yoshitsugu Tajima
Nov 10, 2018·Canadian Journal of Physiology and Pharmacology·Sherif S HassanZulfiqar Ahmad
Jul 19, 2019·Oxidative Medicine and Cellular Longevity·Graziella RodriguesNorma Possa Marroni
Dec 27, 2018·Transplantation·Mónica B Jiménez-CastroCarmen Peralta
Feb 17, 2021·Nature Reviews. Gastroenterology & Hepatology·Jordi Gracia-SanchoRubén Francés

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