Viral gene delivery of superoxide dismutase attenuates experimental cholestasis-induced liver fibrosis in the rat

Zhong, Zhi; Froh, Matthias; Wheeler, Michael D.; Smutney, Olivia M; Lehmann, Thorsten G.; Thurman, Ronald G.

doi:10.1038/sj.gt.3301638

Cited by 57 publications

(53 citation statements)

References 44 publications

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“…NF-κB/DNA complexes were barely detectable in livers from sham-operated rats (independently of pretreatment) but increased around 3.5-fold after BDL, consistent with our previous studies [29,30] . CoPP pretreatment did not suppress this activation (data not shown).…”

Section: Transcription Factors and Cytokine Expression In The Liversupporting

confidence: 80%

“…The supernatant was collected and used as the source of protein for Western blots, as described elsewhere [29,30] . Protein was analyzed using a 1:1000 dilution of anti-HO-1 polyclonal antibody (Santa Cruz Biotechnology, Santa Cruz, CA, USA) and a 1:5000 dilution of horseradish peroxidase-conjugated antibody (Amersham Pharmacia Biotech, Piscataway, NJ, USA).…”

Section: Protein Isolation and Western Blottingmentioning

confidence: 99%

“…Protein was analyzed using a 1:1000 dilution of anti-HO-1 polyclonal antibody (Santa Cruz Biotechnology, Santa Cruz, CA, USA) and a 1:5000 dilution of horseradish peroxidase-conjugated antibody (Amersham Pharmacia Biotech, Piscataway, NJ, USA). AP-1 and NF-κB determination using EMSA Measurement of AP-1 and NF-κB by EMSA was performed, as described in detail elsewhere [29][30][31] .…”

Section: Protein Isolation and Western Blottingmentioning

confidence: 99%

“…The RNA was extracted and purified following standard phenol/ chloroform extraction and ethanol precipitation. RNase protection assays were performed using the RiboQuant multiprobe assay system (Pharmingen, San Diego, CA, USA) or an individual probe [29,30] . Gels were visualized by autoradiography [32] .…”

Section: Protein Isolation and Western Blottingmentioning

confidence: 99%

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Heme oxygenase-1 overexpression increases liver injury after bile duct ligation in rats

Froh

Conzelmann²,

Walbrun³

et al. 2007

WJG

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AIM:To investigate the effects of heme oxygenase-1 (HO-1) against oxidant-induced injury caused by bile duct ligation (BDL). METHODS:Either cobalt protoporphyrin (CoPP), a HO-1 inducer, or saline were injected intraperitoneally in male SD-rats. Three days later, BDL or sham-operations were performed. Rats were sacrificed 3 wk after BDL and livers were harvested for histology. Fibrosis was evaluated by sirius red staining and image analysis. Alpha-smooth muscular actin, which indicates activation of stellate cells, was detected by immunohistochemical staining, and cytokine and collagen-Ⅰα (Col-Ⅰα) mRNA expression was detected using RNase protection assays. RESULTS:Serum alanine transaminase increased 8-fold above normal levels one day after BDL. Surprisingly, enzyme release was not reduced in rats receiving CoPP. Liver fibrosis was evaluated 3 wk after BDL and the sirius red-positive area was found to be increased to about 7.8%. However, in CoPP pretreated rats sirius redpositive areas were increased to about 11.7% after BDL. Collagen-Ⅰα and TGF-β mRNA increased significantly by BDL. Again, this effect was increased by HO-1 overexpression.

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Section: Transcription Factors and Cytokine Expression In The Liversupporting

confidence: 80%

Section: Protein Isolation and Western Blottingmentioning

confidence: 99%

Section: Protein Isolation and Western Blottingmentioning

confidence: 99%

Section: Protein Isolation and Western Blottingmentioning

confidence: 99%

See 2 more Smart Citations

Heme oxygenase-1 overexpression increases liver injury after bile duct ligation in rats

Froh

Conzelmann²,

Walbrun³

et al. 2007

WJG

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“…Recent evidence suggests that cholestasis causes liver injury through mechanisms that involve mitochondrial oxidative stress. [33][34][35][36] Accordingly, a decrease in DDAH activity in cholestatic livers, caused by oxidative damage to the enzyme, might explain the increased plasma ADMA levels found in rats with BDE-induced cirrhosis. The possibility that ADMA accumulation is due to mechanical biliary obstruction in rats with BDE-induced cirrhosis, was ruled out by finding undetectable levels of ADMA in bile in this model.…”

Section: Discussionmentioning

confidence: 99%

A role for asymmetric dimethylarginine in the pathophysiology of portal hypertension in rats with biliary cirrhosis

Laleman¹,

Omasta²,

Casteele³

et al. 2005

Hepatology

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Reduced intrahepatic endothelial nitric oxide synthase (eNOS) activity contributes to the pathogenesis of portal hypertension (PHT) associated with cirrhosis. We evaluated whether asymmetric dimethylarginine (ADMA), a putative endogenous NOS inhibitor, may be involved in PHT associated with cirrhosis. Two rat models of cirrhosis (thioacetamide [TAA]-induced and bile duct excision [BDE]-induced, n ‫؍‬ 10 each), one rat model of PHT without cirrhosis (partial portal vein-ligated [PPVL], n ‫؍‬ 10), and sham-operated control rats (n ‫؍‬ 10) were studied. We assessed hepatic NOS activity, eNOS protein expression, plasma ADMA levels, and intrahepatic endothelial function. To evaluate intrahepatic endothelial function, concentration-effect curves of acetylcholine were determined in situ in perfused normal rat livers and livers of rats with TAAor BDE-induced cirrhosis (n ‫؍‬ 10) that had been preincubated with either vehicle or ADMA; in addition, measurements of nitrite/nitrate (NOx) and ADMA were made in perfusates. Both models of cirrhosis exhibited decreased hepatic NOS activity. In rats with TAA-induced cirrhosis, this decrease was associated with reduced hepatic eNOS protein levels and immunoreactivity. Rats with BDE-induced cirrhosis had eNOS protein levels comparable to those in control rats but exhibited significantly higher plasma ADMA levels than those in all other groups. In normal perfused liver, ADMA induced impaired endothelium-dependent vasorelaxation and reduced NOx perfusate levels, phenomena that were mimicked by N G -nitro-L-arginine-methyl ester. In contrast to perfused livers with cirrhosis induced by TAA, impaired endothelial cell-mediated relaxation in perfused livers with cirrhosis induced by BDE was exacerbated by ADMA and was associated with a decreased rate of removal of ADMA (34.3% ؎ 6.0% vs. 70.9% ؎ 3.2%). In conclusion, in rats with TAA-induced cirrhosis, decreased eNOS enzyme levels seem to be responsible for impaired NOS activity; in rats with biliary cirrhosis, an endogenous NOS inhibitor, ADMA, may mediate decreased NOS activity. (HEPATOLOGY 2005;42:1382-1390

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Immunohistochemistry for the detection of renal cell carcinoma in effusion cytology

Chute

Kong

Stelow

2011

Diagnostic Cytopathology

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Renal cell carcinoma (RCC) is known for its unpredictable behavior. RCC rarely involves serosal surfaces and, when present, can be difficult to distinguish from mesothelial cells in cytologic preparations. Immunohistochemical stains are frequently used with effusion cytology; however, RCCs express traditional glandular antigens less frequently than other adenocarcinomas. We investigated the utility of typical immunohistochemical stains for identifying effusion involvement by RCC, along with more specific RCC markers. The cytology databases from two academic institutions were searched for all effusions involved by RCC with retrievable cell-block material. A four-marker immunohistochemical panel we generally use for distinguishing adenocarcinoma from mesothelial proliferations was then applied (calretinin, WT1, MOC31, and B72.3). In addition, each case was stained for RCC antigen, CD10, and PAX2. Eleven cases of RCC involving serous effusions were identified: six conventional clear-cell RCCs, three papillary RCCs, and two RCCs, not otherwise specified. Neoplastic cells were positive for MOC-31 in 3 of 11 cases, RCC antigen in 5 of 11 cases, and CD10 in 10 of 11 cases. RCC cells were negative for B-72.3, WT1, and calretinin in all cases. Background mesothelial cells showed high-background cytoplasmic staining for PAX-2; all RCC tumor cells were negative or equivocal. A conventional panel used for the diagnosis of adenocarcinoma in fluids will fail to detect most cases of metastatic RCC, particularly clear-cell RCC. Additional antibodies, such as those to CD10 and RCC, may be helpful to identify these tumors. PAX2 shows high background in mesothelial cells, which makes interpretation of nuclear staining difficult.

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Viral gene delivery of superoxide dismutase attenuates experimental cholestasis-induced liver fibrosis in the rat

Cited by 57 publications

References 44 publications

Heme oxygenase-1 overexpression increases liver injury after bile duct ligation in rats

Heme oxygenase-1 overexpression increases liver injury after bile duct ligation in rats

A role for asymmetric dimethylarginine in the pathophysiology of portal hypertension in rats with biliary cirrhosis

Immunohistochemistry for the detection of renal cell carcinoma in effusion cytology

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