Morphological signs of cirrhosis regression

Vinicius, Igor Di; Baptista, Ana Paula; Barbosa, Alynne da Silva; Andrade, Zilton A.

doi:10.1016/j.prp.2005.05.009

Cited by 15 publications

(7 citation statements)

References 14 publications

(18 reference statements)

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“…In the placebo group, there was also a rise in the level of MMP-13 and a decline in the level of α -SMA. This is in accordance with a study on natural regeneration that found a reduction in fibrotic septa and a greater size of regenerative nodules during the endogenous regression of the process of cirrhosis [39].…”

Section: Discussionsupporting

confidence: 92%

“…c-Myc and α -FP are oncogene markers known to be highly expressed in various types of cancer, including hepatocellular carcinoma [40–43]. The levels of these markers were significantly increased in the placebo group in relation to the intact group where it presents a low expression of these proliferation markers (plots of amplification in supplementary materials (available here)), which explains the larger size of regenerative nodules detected with histological techniques [39–41, 44]. Further research is needed to clarify the significant rise in the concentration of c-Myc in the group treated with carvedilol.…”

Section: Discussionmentioning

confidence: 99%

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Doxazosin and Carvedilol Treatment Improves Hepatic Regeneration in a Hamster Model of Cirrhosis

Salas

Navarro‐Gonzalez

Martínez-Hernández

et al. 2018

BioMed Research International

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Regulation of the mechanisms of fibrosis is an important goal in the treatment of liver cirrhosis. One mechanism is the participation of hepatic stellate cells in fibrogenesis when activated by catecholamines. Consequently, α/β adrenoblockers are proposed as an alternative treatment for chronic liver lesions such as fibrosis and/or cirrhosis and for possible liver regeneration. We herein analyzed the effect of doxazosin and carvedilol treatments during the regeneration of tissue in a hamster model of liver cirrhosis. Tissue samples were examined by H&E and PAS to evaluate tissue damage and with Sirius red to assess collagen fiber content. ALT, AST, albumin, and total proteins were examined by spectrophotometry. Determination of the levels of α-SMA and TGF-β in hepatic tissue was examined by Western blot and of the expression of TIMP-2, MMP-13, α-FP, HGF, CK-7, and c-Myc was examined by qPCR. Treatment with doxazosin or carvedilol prompted histological recovery and reduced collagen fibers in the livers of cirrhotic hamsters. The expression of TIMP-2 decreased and that of MMP-13 increases in animals treated with adrenoblockers with respect to the group with cirrhosis. Additionally, the concentration of α-SMA and TGF-β declined with both drugs with respect to placebo p<0.05. On the other hand, each drug treatment led to a distinct scenario for cell proliferation markers. Whereas doxazosin produced no irregularities in α-FP, Ki-67, and c-Myc expression, carvedilol induced an increment in the expression of these markers with respect to the intact. Hence, doxazosin and carvedilol are potential treatments for the regression of hepatic cirrhosis in hamsters in relation to the decrease of collagen in the hepatic parenchyma. However, at regeneration level we observed that doxazosin caused slight morphological changes in hepatocytes, such as its balonization without affecting the hepatic function, and on the other hand, carvedilol elicited a slight irregular expression of cell proliferation markers.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Doxazosin and Carvedilol Treatment Improves Hepatic Regeneration in a Hamster Model of Cirrhosis

Salas

Navarro‐Gonzalez

Martínez-Hernández

et al. 2018

BioMed Research International

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“…This result corroborates with previous histopathological findings that cirrhosis is not fully reversible especially with regard to the changes in liver microvasculature [20]. The inability of the remodeled vasculature to returning to its original form is possibly due to the complexity of the angio-architecture, and the fundamental changes that it undergoes during the development of cirrhosis [20], [21]. It is worth mentioning that our DEI image results are directly proportional to the results of immunohistochemistry staining of CD34.…”

Section: Discussionsupporting

confidence: 91%

“…With the aid of DEI, we first re-confirm previous pathological findings such as the increase in angiogenesis over time during fibrogenesis [3], [19]. Furthermore, during the regression phase of cirrhosis the quantity of blood vessels does in fact decrease but fails to completely return to normalcy [20], [21]. This result corroborates with previous histopathological findings that cirrhosis is not fully reversible especially with regard to the changes in liver microvasculature [20].…”

Section: Discussionsupporting

confidence: 88%

A New Conversation between Radiology and Pathology-Identifying Microvascular Architecture in Stages of Cirrhosis via Diffraction Enhanced Imaging In Vitro

Chen

Bihi

et al. 2014

PLoS ONE

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Background/AimDiffraction enhanced imaging (DEI) is a synchrotron radiation X-ray phase-contrast imaging technique that can better reveal the microstructure of biological soft tissues than conventional X-rays. The aim of this study is to investigate the angio-architectural changes of the liver during fibrosis, cirrhosis and its subsequent regression by applying synchrotron radiation based DEI.MethodsDEI experiments were performed at the 4W1A station of Beijing Synchrotron Radiation Facility. Twenty-four Sprague-Dawley rats were induced with liver fibrosis by carbon tetrachloride (CCl4) for up to 10 weeks, after which spontaneous regression started and continued until week 30. Quantitative analysis of the DEI images yielded the mean vascular density and intercapillary distance, which was then re-confirmed by immunohistochemical analysis of CD34.ResultsBased on the DEI results, the mean vascular density was 1.4-fold higher in fibrotic rats (at week 6) and 2-fold higher in cirrhotic rats (at week 10) compared with the control (p<0.05). Accordingly, the intercapillary distance decreased to 563.89±243.35 µm in fibrotic rats and 392.90±92.68 µm in cirrhotic rats compared with 673.85±214.16µm in the control (p<0.05). During fibrosis regression at week 30, vascular density was 0.7-fold lower and intercapillary distance increased to 548.60±210.94 µm as compared with cirrhotic rats (p<0.05).In parallel to the DEI results, immunohistochemical analysis of CD34 showed similar changes.ConclusionSynchrotron-based DEI can conduct radiological as well as pathological analysis. Our results are consistent with previous reports indicating that angiogenesis is directly proportional to fibrosis progression. Furthermore, by clarifying the vascular characteristics of liver diseases, DEI reveals that cirrhosis cannot fully reverse during fibrosis regression.

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“…Moreover, it is established that ECM self-degradation and reversibility of liver brosis are achievable upon removal of the damaging agent. It is noteworthy that after removal of the cause of brosis, the liver tissue can adapt to a new structure to ensure its normal functioning, making brosis clinically but not morphologically reversible [33,34].…”

Section: Discussionmentioning

confidence: 99%

Influence of Xymedon and its conjugate with L-ascorbic acid on collagen remodeling in the liver fibrosis rat model

Belyaev,

Vyshtakalyuk,

Parfenov

et al. 2024

Preprint

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Fibrosis of the liver is a chronic inflammatory process with activation of hepatic stellate cells and abnormal accumulation of proteins in the extracellular matrix. However, it is known that pyrimidine derivatives have a beneficial effect on the condition of various organs with the ongoing process of fibrosis. Therefore, the aim of this work was to investigate the effect of the drug Xymedon (1,2-dihydro-4,6-dimethyl-1-N-(2-hydroxyethyl)pyrimidine-2-one, (compound 1) and its conjugate with L-ascorbic acid (compound 2) on collagen remodeling in rat liver tissue. For this purpose, female Wistar rats were used to model fibrosis by oral administration of carbon tetrachloride (CCl4) and ethanol for 8 weeks. Then the rats were treated with the studied compounds for 2 or 4 weeks. Histological analysis by hematoxylin-eosin and Van Gizon’s staining of liver slices, biochemical analysis of blood serum and Western blot analysis of COX-2 level in rat liver homogenates were performed. It has been shown that in the control group without treatment, after 2 weeks of withdrawal of CCl4 + ethanol, collagen remodeling occurs to the certain chronic level. At the same time, compound 2 reduces the level of collagen fibers by 41% compared to the control group, while native compound 1 has no such effect. Also, in all groups studied, there was the decrease in the inflammatory marker COX-2 both after 2 weeks of CCl4 + ethanol withdrawal and after treatment with studied compounds 1 and 2. Thus, compound 2 (conjugate of Xymedon with L-ascorbic acid) has the greater antifibrotic effect on the rat liver fibrosis model compared to the native molecule of compound 1 (Xymedon). At the same time, this effect is not associated with the level of COX-2.

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Morphological signs of cirrhosis regression

Cited by 15 publications

References 14 publications

Doxazosin and Carvedilol Treatment Improves Hepatic Regeneration in a Hamster Model of Cirrhosis

Doxazosin and Carvedilol Treatment Improves Hepatic Regeneration in a Hamster Model of Cirrhosis

A New Conversation between Radiology and Pathology-Identifying Microvascular Architecture in Stages of Cirrhosis via Diffraction Enhanced Imaging In Vitro

Influence of Xymedon and its conjugate with L-ascorbic acid on collagen remodeling in the liver fibrosis rat model

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