Increased periportal oxidative injury in acute cholestasis.

Tissue sections from sham and BDL mice were probed immunohistochemically for pH2Ax and 4-HNE. N = 4/group, 200X, PT-portal triad, CV-Central vein. Arrows indicate area of increased staining.</p

Increased expression of autophagic proteins in acute murine cholestasis.

A. qPCR analysis of mRNA for autophagic proteins in liver tissue isolated from 3-day sham and BDL adult mice (N = 5/group). Expression was normalized against HPRT. B. Western analysis of autophagic proteins in liver tissue isolated from BDL mice (N = 5/group). Blots were normalized to GAPDH expression. C. qPCR analysis of mRNA for autophagic proteins in liver tissue isolated from 10-week old Mdr2KO mice (N = 4/group). D. Western analysis of autophagic proteins in liver tissue isolated from 10 week on Mdr2KO mice (N = 6/group). Blots were normalized to GAPDH expression Data are presented as Mean ± STDEV and were statistically analyzed using a Student’s t-test, *p<0.05, **p<0.01, ***P<0.001, ****p<0.0001, N = 6/group.</p

Serum biochemical analysis of liver injury in WT and BDL treated mice.

Aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, total bilirubin and total serum bile acid concentrations. Data were analyzed statistically using a Student’s t-test and are presented as Mean ± STDEV, ***p (TIF)</p

Fig 8 -

Colocalization of p62 and 4-HNE in liver in cholestasis A. Control and PSC liver (200X). B. Sham and BDL cholestatic liver (100X) C. WT and Mdr2KO liver (100X). Arrows indicate periportal hepatocytes of increased staining/colocalization. n = 4/group, Blue-Dapi, Green-4-HNE, Cyan-p62. CV-central vein, PT-portal triad.</p

Serum biochemical parameters of human PSC patients.

Serum biochemical parameters of human PSC patients.</p

Histochemical assessment of liver injury and ductular proliferation in C57BL/6 sham and 3-day BDL mice.

A. Hematoxylin and Eosin (H&E) 200X. B. Picrosirius Red (PSR) 100X. C. Cytokeratin 7 (CK7) 200X. CV-central vein, PT-portal triad, NEC-necrosis, n = 4/group. (TIF)</p

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Increased periportal nuclear localization of Nrf2 in human and murine cholestasis.

Tissue sections were examined for Nrf2 nuclear localization A. Normal human liver, PSC (200X). B. Sham mice and BDL mice (100X). C. Accumulation of ubiquitinated proteins in parenchymal cells surrounding the injured portal triad in PSC. n = 3-4/group, (200X). CV-central vein, PT-portal triad. Arrows indicate increased periportal staining.</p

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Quantification of necrosis, fibrosis, H2Ax positive nuclei and the ductular reaction (CK7), in liver tissue from C57BL/6 sham and 3-day BDL mice.

A. Percent necrotic injury. B. Quantification of Picrosirius red staining (PSR). C. Percent cytokeratin 7 (CK7) positive cells. D. qPCR analysis of mRNA for fibrogenic genes Timp1 and Col1a1 in liver tissue from control and 3D BDL mouse liver (N = 4/group). E. H2Ax positive nuclei/100X field. Data were statistically analyzed using Student’s t-test and are presented as Mean ± STDEV. ****p (TIF)</p