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Biochem Biophys Res Commun. 2014 Jul 18;450(1):773-6. doi: 10.1016/j.bbrc.2014.06.048. Epub 2014 Jun 19.

Ethanol affects hepatitis C pathogenesis: humanized SCID Alb-uPA mouse model.

Author information

1
Research Service, Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, NE, USA; Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68105, USA. Electronic address: nosna@unmc.edu.
2
Research Service, Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, NE, USA; Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68105, USA.
3
Department of Surgery, University of Nebraska Medical Center, Omaha, NE 68105, USA.
4
Research Service, Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, NE, USA; Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68105, USA.
5
Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68105, USA.

Abstract

Alcohol consumption exacerbates the course of hepatitis C viral (HCV) infection, worsens outcomes and contributes to the development of chronic infection that exhibits low anti-viral treatment efficiency. The lack of suitable in vivo models makes HCV-ethanol studies very difficult. Here, we examine whether chimeric SCID Alb-uPA mice transplanted with human hepatocytes and infected with HCV develop worsening pathology when fed ethanol. After 5 weeks of feeding, such mice fed chow+water (control) or chow+20% ethanol in water (EtOH) diets mice developed oxidative stress, decreased proteasome activity and increased steatosis. Importantly, HCV(+) mice in the control group cleared HCV RNA after 5 weeks, while the infection persisted in EtOH-fed mice at the same or even higher levels compared with pre-feeding HCV RNA. We conclude that in chimeric SCID Alb-uPA mice, EtOH exposure causes the complex biochemical and histological changes typical for alcoholic liver injury. In addition, ethanol feeding delays the clearance of HCV RNA thereby generating persistent infection and promoting liver injury. Overall, this model is appropriate for conducting HCV-ethanol studies.

KEYWORDS:

Alcohol; Hepatitis C virus; Oxidative stress; Proteasome activity; SCID Alb-uPA mice

PMID:
24953695
DOI:
10.1016/j.bbrc.2014.06.048
[Indexed for MEDLINE]
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