11 research outputs found

    Vitamin E Attenuates the Progression of Non-Alcoholic Fatty Liver Disease Caused by Partial Hepatectomy in Mice.

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    The progression of non-alcoholic fatty liver disease (NAFLD) likely involves a 'multiple hit' mechanism. We hypothesized that partial hepatectomy, a procedure performed frequently in patients with NAFLD, would accelerate the progression of disease.C57BL/6JolaHsd mice were fed a choline-deficient L-amino acid-defined diet (CD-AA) or a choline-sufficient L-amino acid-defined control diet (CS-AA). Part of the mice in the CD-AA group received a diet enriched in vitamin E (~20 mg /day). Two weeks after the start of the diet, mice underwent a partial hepatectomy or a sham operation.In the CD-AA group, NAFLD activity scores were significantly higher at 7 days after partial hepatectomy compared to the sham operated mice (3.7 ± 1.3 vs. 1.8 ± 0.7; P<0.05). In addition, TBARS, a measure for oxidative stress, in liver tissue of the CD-AA group were significantly higher at day 1, 3 and 7 after partial hepatectomy compared to the sham operated mice (P<0.05). Vitamin E therapy significantly reduced TBARS level at day 7 after partial hepatectomy compared to the CD-AA diet group (P< 0.05). Vitamin E suppletion reduced NAFLD activity score at day 7 after partial hepatectomy compared to the CD-AA group (2.3 ± 0.8 vs. 3.8 ± 1.0; P<0.05).Partial hepatectomy accelerates the progression of NAFLD. Disease progression induced by partial hepatectomy is substantially attenuated by vitamin E

    Vitamin E attenuates the progression of NAFLD after partial hepatectomy.

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    <p>(A) Hematoxylin and eosin staining of paraffin embedded-liver sections of mice on a CD-AA diet (right panel) or vitamin E enriched CD-AA diet (left panel) at day 7 after a partial hepatectomy (Magnification, X 200). (B) Graph represents the NAFLD activity scores in mice on a CD-AA diet or vitamin E enriched CD-AA diet at day 7 after a partial hepatectomy (n = 9 per group). (C) Graph represents the TBARS levels in the liver tissue at 7 days after a partial hepatectomy or a sham operation (n = 9 per group) in mice on CD-AA diet and vitamin E enriched CD-AA diet. Malondialdehyde (MDA) was used as standard. * P < 0.05 for CD-AA vs. vitamin E enriched CD-AA at day 7 after operation. (D) Graph represents the mRNA expression level of hemoxygenase-1 (HO-1) in the liver tissue at day 7 after a partial hepatectomy or a sham operation in mice on CS-AA diet (n = 6), CD-AA diet (n = 15) and vitamin E enriched CD-AA diet (n = 9). P< 0.05 for CD-AA vs Vitamin E enriched CD-AA at day 7 after operation.</p

    The choline-deficient L-amino acid-defined diet (CD-AA) induces mild steatosis by 3 weeks.

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    <p>(A) Hematoxylin and eosin staining of paraffin-embedded liver sections of mice on a CD-AA diet (right panel) and control diet (CS-AA, left panel) by 3 weeks (Magnification, X 100). (B) Liver-to-body weight ratios of mice on a CD-AA diet or a CS-AA diet by 3 weeks (n = 9). (C) Plasma levels of ALT and (D) AST in mice on a CD-AA diet or a CS-AA diet by 3 weeks (n = 9).</p

    Partial hepatectomy accelerates the progression of NAFLD.

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    <p>(A) Hematoxylin and eosin staining of paraffin embedded-liver sections of mice on a CD-AA diet at day 7 after a partial hepatectomy (right panel) or a sham operation (left panel) (Magnification, X 200). (B) Graph represents the NAFLD activity scores in mice on a CD-AA diet at day 7 after a partial hepatectomy or a sham operation (n = 6 per group). (C) Graph represents the TBARS levels in the liver tissue at different time points after a partial hepatectomy (n = 6 per group) or a sham operation (n = 3 per group) in mice on CD-AA diet and CS-AA diet. Malondialdehyde (MDA) was used as standard. * P < 0.05 for CD-AA vs. CS-AA at day 1, day 3 and day 7 after partial hepatectomy, respectively.</p

    Mild steatosis does not impair liver regeneration after partial hepatectomy.

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    <p>(A) Graph represents the restoration of liver mass over the 7-days duration after partial hepatectomy. (B) Immunohistochemical staining of Ki-67 (yellow arrows show ki-67 positive cells) in mice on a CD-AA diet (right panel) or a CS-AA diet (left panel) at day 3 after hepatectomy (Magnification, X 200). Graph represents the number of nuclei positive for Ki-67 relative to the total nuclei stained with hematoxylin at day 3 after hepatectomy. At least six random high power fields were counted for each mouse. (C) Plasma levels of ALT and (D) AST in mice on a CD-AA diet or a CS-AA diet at different time points after hepatectomy (n = 6 per time point).</p

    Diffuse reflectance spectroscopy accurately quantifies various degrees of liver steatosis in murine models of fatty liver disease

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    Background: A real-time objective evaluation for the extent of liver steatosis during liver transplantation is currently not available. Diffuse reflectance spectroscopy (DRS) rapidly and accurately assesses the extent of steatosis in human livers with mild steatosis. However, it is yet unknown whether DRS accurately quantifies moderate/severe steatosis and is able to distinguish between micro-and macrovesicular steatosis. Methods: C57BL/6JolaHsd mice were fed wit a choline-deficient l-amino acid-defined diet (CD-AA) or a choline-sufficient l-amino acid-defined control diet (CS-AA) for 3, 8, and 20 weeks. In addition B6. V-Lepob/OlaHsd (ob/ob) mice and their lean controls were studied. A total of 104 DRS measurements were performed in liver tissue ex vivo. The degree of steatosis was quantified from the DRS data and compared with histopathological analysis. Results: When assessed by histology, livers of mice fed with a CD-AA and CS-AA diet displayed macrovesicular steatosis (range 0-74 %), ob/ob mice revealed only microvesicular steatosis (range 75-80 %), and their lean controls showed no steatosis. The quantification of steatosis by DRS correlated well with pathology (correlation of 0.76 in CD-AA/CS-AA fed mice and a correlation of 0.75 in ob/ob mice). DRS spectra did not distinguish between micro-and macrovesicular steatosis. In samples from CD-AA/CS-AA fed mice, the DRS was able to distinguish between mild and moderate/severe steatosis with a sensitivity and specificity of 86 and 81 %, respectively. Conclusion: DRS can quantify steatosis with good agreement to histopathological analysis. DRS may be useful for real-time objective evaluation of liver steatosis during liver transplantation, especially to differentiate between mild and moderate/severe steatosis
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