Simvastatin Attenuates Liver Injury in Rodents with Biliary Cirrhosis Submitted to Hemorrhage/Resuscitation.

Meireles, Cintia Zimmermann; Pasarin, Marcos; Lozano, Juan Jose; García-Calderó, Héctor; Gracia-Sancho, Jordi; García-Pagán, Juan Carlos; Bosch, Jaime; Abraldes, Juan G (2017). Simvastatin Attenuates Liver Injury in Rodents with Biliary Cirrhosis Submitted to Hemorrhage/Resuscitation. Shock, 47(3), pp. 370-377. Lippincott Williams & Wilkins 10.1097/SHK.0000000000000734

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Liver function deterioration is a major cause of death in variceal bleeding. The effects of bleeding on intrahepatic microvascular dysfunction, which contributes to liver injury in cirrhosis, are largely unknown. The aims of this study were to evaluate the impact of hemorrhage/resuscitation (H/R) on cirrhotic microcirculation, and whether simvastatin, a drug that improves liver microcirculation, has hepatoprotective effects. The study was performed in three groups of rats: controls, rats with biliary cirrhosis (CBDL) and CBDL rats pre-treated with 3 doses (5 mg*Kg-1*day-1) of simvastatin. Rats were submitted to H/R or sham procedure. Subsequently, livers were isolated and perfused for functional assessment of liver microcirculation. Liver transcriptome was assessed with microarrays. H/R significantly impaired endothelial-dependent vasorelaxation in cirrhotic (p = 0.035) but not control livers. H/R induced a similar increase in ALT in control and cirrhotic rats, whereas the increase in AST was 10 times higher in cirrhotic than in control rats (p = 0.007). Simvastatin prevented the impairment in endothelial-dependent vasorelaxation induced by H/R, and reduced by half the increase in ALT and AST (p < 0.05). Transcriptomics showed a marked upregulation of genes related to inflammatory response after H/R in cirrhotic livers, but not in controls, and this was blunted by simvastatin. In conclusion, H/R aggravates liver microvascular dysfunction in cirrhosis, and upregulates liver inflammatory pathways. This does not occur in control livers. Simvastatin prevented H/R-induced liver endothelial dysfunction, and attenuated liver injury and liver inflammatory response, suggesting that it might have potential for protecting the cirrhotic liver during bleeding complications.

Item Type:	Journal Article (Original Article)
Division/Institute:	04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine > Hepatology 04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Hepatologie 04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Hepatologie 04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine
UniBE Contributor:	Bosch, Jaime
Subjects:	600 Technology > 610 Medicine & health
ISSN:	1073-2322
Publisher:	Lippincott Williams & Wilkins
Language:	English
Submitter:	Lilian Karin Smith-Wirth
Date Deposited:	05 Apr 2017 15:25
Last Modified:	02 Mar 2023 23:28
Publisher DOI:	10.1097/SHK.0000000000000734
PubMed ID:	27559696
URI:	https://boris.unibe.ch/id/eprint/93614