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Volume 123, Issue 1, Pages (July 2002)

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1 Volume 123, Issue 1, Pages 325-335 (July 2002)
The importance of cycling of blood alcohol levels in the pathogenesis of experimental alcoholic liver disease in rats  Fawzia Bardag–Gorce, Barbara A. French, Jun Li, Nora E. Riley, Qi X. Yuan, Vimonrat Valinluck, Paul Fu, Magnus Ingelman–Sundberg, Seokjoo Yoon, Samuel W. French  Gastroenterology  Volume 123, Issue 1, Pages (July 2002) DOI: /gast Copyright © 2002 American Gastroenterological Association Terms and Conditions

2 Fig. 1 The UALs of 9 rats fed ethanol with low UAL (trough) and 11 rats with high UAL (peak) were correlated with BALs of the same rats and regression analysis of this data shown. R = 0.972, P < Gastroenterology  , DOI: ( /gast ) Copyright © 2002 American Gastroenterological Association Terms and Conditions

3 Fig. 2 Photomicrographs of a control (A), a peak (B), and a trough (C). (H&E; original magnification 156×). Note the inflammation in the liver at the peak (arrow). Gastroenterology  , DOI: ( /gast ) Copyright © 2002 American Gastroenterological Association Terms and Conditions

4 Fig. 3 Rat liver quantitation of VEGF by Western blot. VEGF was significantly increased (20%) at the peaks (P vs. T, P < 0.018; P vs. control, P < 0.036; n = 5). Gastroenterology  , DOI: ( /gast ) Copyright © 2002 American Gastroenterological Association Terms and Conditions

5 Fig. 4 Rat liver quantitation of c-fos by Western blot. Levels of this early-response gene product were significantly decreased at the peaks compared with the troughs (P < 0.023, n = 4–8). Gastroenterology  , DOI: ( /gast ) Copyright © 2002 American Gastroenterological Association Terms and Conditions

6 Fig. 5 Western blot analysis of the ADH levels. There were no significant differences (P < 0.341, n = 5–8). Gastroenterology  , DOI: ( /gast ) Copyright © 2002 American Gastroenterological Association Terms and Conditions

7 Fig. 6 Western ADH-1 analysis of the ADH-1 levels. There were no significant differences. Gastroenterology  , DOI: ( /gast ) Copyright © 2002 American Gastroenterological Association Terms and Conditions

8 Fig. 7 Northern blot of mRNA for ADH class I was significantly increased in both the peaks and troughs compared to controls (*P < 0.001; $P < 0.009). The peaks were not significantly different from the troughs. Gastroenterology  , DOI: ( /gast ) Copyright © 2002 American Gastroenterological Association Terms and Conditions

9 Fig. 8 Western blot analysis of the CYP2E1 levels. Both the peak and trough levels are significantly increased compared with controls (*,$P < 0.001, n = 5–8). Gastroenterology  , DOI: ( /gast ) Copyright © 2002 American Gastroenterological Association Terms and Conditions

10 Fig. 9 Chymotrypsin-like activity in the liver cytosolic fraction of rats fed ethanol. Note that the activity was significantly lower at both the peaks and troughs (*,$P < 0.05, n = 5). Gastroenterology  , DOI: ( /gast ) Copyright © 2002 American Gastroenterological Association Terms and Conditions

11 Fig. 10 NADH levels markedly increased at the peaks compared with the troughs and control levels (*P < 0.001; $P < 0.03; n = 5). Gastroenterology  , DOI: ( /gast ) Copyright © 2002 American Gastroenterological Association Terms and Conditions

12 Fig. 11 The NADH/NAD ratio in the liver at the peaks and troughs of the UAL cycle. The results were significantly higher at the peaks compared to the troughs and controls (*P < 0.001; $P < 0.001; n = 5). Gastroenterology  , DOI: ( /gast ) Copyright © 2002 American Gastroenterological Association Terms and Conditions

13 Fig. 12 Liver ATP levels from rats fed ethanol. A significant decrease was observed at the peaks compared to the troughs and controls (*P < 0.002; $P < 0.001; n = 5). Gastroenterology  , DOI: ( /gast ) Copyright © 2002 American Gastroenterological Association Terms and Conditions

14 Fig. 13 Liver myeloperoxidase positive neutrophils in the sinusoids (number/mm2). The number of neutrophils was significantly decreased at the troughs compared with the controls (*P < 0.015) and nearly significant ($P < 0.051) at the peaks (n = 9–11). Gastroenterology  , DOI: ( /gast ) Copyright © 2002 American Gastroenterological Association Terms and Conditions

15 Fig. 14 Pimonidazole adduct formation in liver sections stained with an antibody labeled with Texas red. The control (A) shows centrilobular positive staining. There was an increase in the fluorescent intensity in the periportal zone at the peak (B) compared to the trough (C) and the controls. (Original magnification 152×). Gastroenterology  , DOI: ( /gast ) Copyright © 2002 American Gastroenterological Association Terms and Conditions

16 Fig. 15 Pimonidazole adduct formation in liver sections stained with an antibody labeled with Texas red is quantitated by measuring the immunofluorescence of stained periportal hepatocytes. Fluorescence was measured blinded as to the animal treatment in 5 separate periportal areas from multipled liver sections, and the results were averaged. There was a significant increase of fluorescence in the high-UAL rats (peak) compared to controls (P vs. C, P = 0.025, n = 4 controls, 5 troughs, and 6 peaks, SEM). The fluorescence was not significantly different between the peaks and the low-UAL rats (troughs), P = Statistical comparisons were made using 1-way ANOVA and an all-pairwise multiple comparison procedure (Student–Newman–Keuls test). Gastroenterology  , DOI: ( /gast ) Copyright © 2002 American Gastroenterological Association Terms and Conditions

17 Fig. 16 This scheme is offered as a possible explanation for the difference in liver pathology manifested at the peaks and troughs of the BAL cycle. Data supporting the changes shown in the boxes are derived from references 1 and 37 and this report. The changes noted in parentheses are hypothetical. Gastroenterology  , DOI: ( /gast ) Copyright © 2002 American Gastroenterological Association Terms and Conditions


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