Basic–Liver, Pancreas, and Biliary TractAbrogation of the Antifibrotic Effects of Natural Killer Cells/Interferon-γ Contributes to Alcohol Acceleration of Liver Fibrosis
Section snippets
Mice
C57BL/6N mice were purchased from the National Cancer Institute (Frederick, MD). All mice used in the present study were housed in a specific pathogen-free facility and were cared for in accordance with National Institutes of Health guidelines.
Chronic Ethanol Consumption and Liver Fibrosis Induced by CCl4
Male C57BL/6N mice weighing ≈25 g were fed a nutritionally adequate liquid diet containing 5% ethanol or a pair-fed diet in which ethanol was substituted isocalorically with dextrin maltose (BioServ, Frenchtown, NJ). Ethanol was introduced gradually by
Ethanol Feeding Decreases HSC Apoptosis and Accelerates Liver Fibrosis During CCl4-Induced Liver Fibrogenesis
Figure 1A shows that injection with 0.1 mL/kg CCl4 induced higher levels of serum ALT in ethanol-fed mice than in pair-fed mice. To generate similar levels of liver injury in both groups, we injected pair-fed mice with a higher dose of CCl4 (0.25 mL/kg). Our results showed that injection with 0.25 mL/kg CCl4 in pair-fed mice caused a similar elevation of serum ALT levels compared with injecting 0.1 mL/kg CCl4 in ethanol-fed mice (Figure 1A). Next, we compared liver fibrosis in these mice (
Discussion
Chronic alcohol consumption is one of the main causes of accelerated liver fibrosis in patients with viral hepatitis.5, 6, 7, 8, 9 In rodents, ethanol feeding was also shown to accelerate CCl4-induced liver fibrosis.10 It is generally believed that ethanol feeding enhances CCl4 metabolism by induction of cytochrome P450 2E1 expression and, subsequently, enhances CCl4-induced liver injury. Here, we also confirmed that injection of the same dose of CCl4 induced more fibrosis in ethanol-fed mice
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All authors declare that they have no conflict of interest to disclose.
Supported by the intramural program of National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health.