2018
DOI: 10.1159/000489986
|View full text |Cite
|
Sign up to set email alerts
|

Anti-Inflammatory Effects of Vardenafil Against Cholestatic Liver Damage in Mice: a Mechanistic Study

Abstract: Background/Aims: Phosphodiesterase-5 inhibitors have beneficial effects in multiple liver diseases possibly through the reduction of oxidative stress and inflammatory response. However, these effects have not yet been examined in cholestatic liver dysfunction. Hence, this study aimed to explore the ability of vardenafil, a known phosphodiesterase-5 inhibitor, to repress lithocholic acid (LCA)-induced cholestatic liver injury and investigate the possible molecular pathways. Methods: Male Swiss albino mice were … Show more

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...
1
1
1
1

Citation Types

1
20
0

Year Published

2018
2018
2023
2023

Publication Types

Select...
6

Relationship

1
5

Authors

Journals

citations
Cited by 18 publications
(21 citation statements)
references
References 43 publications
1
20
0
Order By: Relevance
“…Previous studies that have supported this hypothesis have used hydrophobic bile acid species such as chenodeoxycholic acid and lithocholic acid at high concentrations that are not seen in cholestatic patients or animal models and thus are likely to be artifacts of these in vitro conditions. 7,8,23 The major species of endogenous bile acids are conjugated bile acids that require bile acid transport proteins to enter cells. These transporters are only seen in hepatic parenchymal cells and are absent in macrophages and other hepatic cells.…”
Section: Discussionmentioning
confidence: 99%
See 1 more Smart Citation
“…Previous studies that have supported this hypothesis have used hydrophobic bile acid species such as chenodeoxycholic acid and lithocholic acid at high concentrations that are not seen in cholestatic patients or animal models and thus are likely to be artifacts of these in vitro conditions. 7,8,23 The major species of endogenous bile acids are conjugated bile acids that require bile acid transport proteins to enter cells. These transporters are only seen in hepatic parenchymal cells and are absent in macrophages and other hepatic cells.…”
Section: Discussionmentioning
confidence: 99%
“…7 However, it must be stressed that the cells in all of these studies were treated with bile acids that either were not the major endogenous bile acid in mouse or used concentrations that were not physiologically or pathophysiologically relevant. Nevertheless, the Nlrp3 inflammasome could be activated in liver tissue in a mouse model of lithocholic acid induced cholestasis, 8 while elevated messenger RNA (mRNA) expression of IL1R1, NLRP3, and caspase-1 was also observed in the liver of patients with biliary atresia. 9 Loss of Il-1r1 or Nlrp3, but not of the Caspase-1 gene, reduced bile duct injury in a mouse model of biliary atresia induced by rotavirus infection.…”
mentioning
confidence: 99%
“…The formalin‐fixed paraffin blocks of liver and heart of all animals were used to construct a tissue miniarray (TmA). Immunohistochemical (IHC) staining was performed on 4‐µm slices of paraffin‐embedded TmA tissue sections using primary antibodies against NF‐κB (p65) and iNOS (Santa Cruz Biotechnology, Santa Cruz, CA) automatically using Ventana Bench Mark XT system (Ventana Medical Systems, Tucson, AZ) as previously described …”
Section: Methodsmentioning
confidence: 99%
“…The excised livers were rinsed in ice-cold physiological saline and automatically using Ventana Bench Mark XT system (Ventana Medical Systems, Tucson, AZ) as previously described. [19]…”
Section: Lipid Peroxidation and Antioxidant Markersmentioning
confidence: 99%
“…Interestingly, treatment of mice with Davanat, a registered inhibitor of Galectin-3 that is currently being studied in clinical trials, determined a significant reduction in inflammasome activation and biliary damage in a model of autoimmune cholangitis [99]. Vardenafil, a phosphodiesterase-5 inhibitor, has been shown to significantly reduce the expression of Nlrp3 and inflammasome components in a cholestatic murine model induced by lithocolic acid administration [100]. Finally, a significant reduction in Nlrp3 inflammasome activation has been demonstrated in the liver tissue of BDL rats subjected to treatment with a saline solution enriched with methane, which has been previously demonstrated to possess anti-oxidative and anti-inflammatory properties [101,102].…”
Section: Inflammasome Activation In Cholestatic Liver Injurymentioning
confidence: 99%