Maraviroc, a CCR5 antagonist, ameliorates the development of hepatic steatosis in a mouse model of non-alcoholic fatty liver disease (NAFLD).

Abstract

OBJECTIVES:

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the general population. The NAFLD spectrum ranges from simple steatosis to cirrhosis. The chemokine CCL5/RANTES plays an important role in the progression of hepatic inflammation and fibrosis. The objective of this study was to examine the effects of maraviroc, a CCR5 antagonist, on liver pathology in a NAFLD mouse model.

METHODS:

A total of 32 male C57BL/6 mice were randomly assigned to one of four groups: (i) control group (chow diet plus tap water); (ii) maraviroc group (chow diet plus maraviroc in drinking water); (iii) high-fat diet (HFD) group (HFD plus tap water); and (iv) maraviroc/HFD group (HFD plus maraviroc). All mice were sacrificed 16 weeks after the beginning of the experiment. Biochemical analyses and liver examinations were performed.

RESULTS:

Mice in the HFD group showed a tendency towards increased body mass gain and liver damage compared with the maraviroc/HFD group. Moreover, liver weight in the HFD group was significantly higher than in the maraviroc/HFD group. Hepatic triglyceride concentration in the maraviroc/HFD group was significantly lower than in the HFD group. Interestingly, the maraviroc/HFD group exhibited a lower degree of steatosis. Furthermore, hepatic CCL5/RANTES expression was significantly lower in the maraviroc/HFD group than in the HFD group. Overall, no differences were observed between the control group and the maraviroc group.

CONCLUSIONS:

Maraviroc ameliorates hepatic steatosis in an experimental model of NAFLD.

• Authors: Laura Pérez-Martínez, Patricia Pérez-Matute, Javier Aguilera-Lizarraga, Susana Rubio-Mediavilla, Judit Narro, Emma Recio, Laura Ochoa-Callejero, José-Antonio Oteo, José-Ramón Blanco
• Journal: The Journal of antimicrobial chemotherapy (J Antimicrob Chemother) Vol. 69 Issue 7 Pg. 1903-10 (Jul 2014) ISSN: 1460-2091 [Electronic] England
• PMID: 24651825 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: [email protected].

Chemical References

• Cyclohexanes
• Triazoles
• Maraviroc

Topics

• Animals
• Cyclohexanes (administration & dosage, adverse effects)
• Disease Models, Animal
• Fatty Liver (pathology)
• Histocytochemistry
• Liver (drug effects)
• Liver Function Tests
• Male
• Maraviroc
• Mice, Inbred C57BL
• Non-alcoholic Fatty Liver Disease (pathology)
• Triazoles (administration & dosage, adverse effects)