Soluble epoxide hydrolase inhibition with t-TUCB alleviates liver fibrosis and portal pressure in carbon tetrachloride-induced cirrhosis in rats - 03/04/18
Benvenuto su EM|consulte, il riferimento dei professionisti della salute.
L'accesso al testo integrale di questo articolo richiede un abbonamento.
| pagine | 8 |
| Iconografia | 5 |
| Video | 0 |
| Altro | 0 |
Summary |
Background/Aims |
Fibrosis and increased intrahepatic vascular resistance are the hallmarks of chronic inflammatory disorders of the liver and cirrhosis. Inhibitors of the enzyme soluble epoxide hydrolase reduce fibrosis in several disease models. The present study aimed at investigating the effects of soluble epoxyhydrolase inhibition with t-TUCB in tetrachloride-induced cirrhosis in rats.
Methods |
The models were established by CCl4 (2ml/kg) given subcutaneously for 14 weeks. t-TUCB was concomitantly administered from the tenth week of modelling time. After the models were successfully built, the rats were anesthetized with sodium phenobarbital and portal pressure was determined in the groups. After that, the rats were killed and part of liver tissues were taken for histological analysis. In addition, the levels of intrahepatic inflammatory message factors were measured using real-time polymerase chain reaction (PCR) analysis. The remaining liver samples were processed for assessment of oxidative stress.
Results |
t-TUCB administration significantly attenuated portal pressure relative to CCl4-only rats. This improvement was associated with decreased deposition of collagen in liver, which was supported by reduced mRNA expression of α-smooth muscle actin (α-SMA), Collagen I, Collagen III, transforming growth factor (TGF)-β and tissue inhibitor of metalloproteinase-1 (TIMP-1) and increased matrix metalloproteinase-1, -13 (MMP-1, -13) mRNA expression. In addition, t-TUCB decreased the levels of proinflammatory cytokines, including IL-1β, IL-6, IL-10, tumor necrosis factor-α (TNF-α) and NF-κB, within cirrhotic hepatic tissue. Meanwhile, oxidative stress was also alleviated following inhibition of sEH in CCl4-induced models, as evidenced by down-regulated levels of malondialdehyde (MDA) and up-regulated levels of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px).
Conclusion |
The soluble epoxyhydrolase inhibitor, t-TUCB alleviates liver fibrosis and portal hypertension through attenuation of inflammatory response and oxidative stress in tetrachloride induced cirrhosis.
Il testo completo di questo articolo è disponibile in PDF.Keywords : Hepatic cirrhosis, Portal hypertension, Soluble epoxide hydrolase, Epoxyeicosatrienoic acids
Abbreviations : PCR, α-SMA, TGF-β, TIMP-1, TNF-α, MDA, SOD, GSH-Px, EETs, sEH, FPP, p-Smad3
Mappa
Vol 42 - N° 2
P. 118-125 - Aprile 2018 Ritorno al numero
Articolo precedente
- Gut microbiota and hypertension: From pathogenesis to new therapeutic strategies
- Yongbo Kang, Yue Cai
- Co-expression of PDGF-B and VEGFR-3 strongly correlates with poor prognosis in hepatocellular carcinoma patients after hepatectomy
- Bin Chen, Jinghua Liu, Xionghua Wang, Qian Shen, Chao Li, Chunshan Dai
Benvenuto su EM|consulte, il riferimento dei professionisti della salute.
L'accesso al testo integrale di questo articolo richiede un abbonamento.
Già abbonato a @@106933@@ rivista ?