The hepatoprotective effect of silibinin after hepatic ischemia/reperfusion in a rat model is confirmed by immunohistochemistry and qRT-PCR

Author(s):  
Afrodite Betsou ◽  
Maria Lambropoulou ◽  
Anastasia-Eirini Georgakopoulou ◽  
Nikolaos Kostomitsopoulos ◽  
Ourania Konstandi ◽  
...  

Abstract Objectives We investigated the positive effect of silibinin after IV administration as silibinin-hydroxypropyl-β-cyclodextrin lyophilized product, by measuring gene expression and liver tissue protein levels of tumor necrosis factor-α, interleukin-6, monocyte chemoattractant protein-1, matrix metalloproteinases matrix metalloproteinases and tissue inhibitor of matrix metalloproteinases-2. Methods 63 Wistar rats of age 13.24±4.40 weeks underwent ischemia/reperfusion (I/R) injury of the liver. The animals were randomized into three groups: Sham (S; n = 7); Control (C; n-28); silibinin (Si; n-28). The C and Si groups underwent 45 min ischemia. Si received silibinin-hydroxypropyl-β-cyclodextrin intravenously immediately before reperfusion at a dose of 5 mg/kg. Both groups were further divided into 4 subgroups, based on euthanasia time (i.e., 60, 120, 180 and 240 min). Key findings qRT-PCR results confirmed the statistically significant reduction of the expression of the pro-inflammatory factors at 240 min after I/R injury (tumor necrosis factor-α: P < 0.05; MCR1: P < 0.05) and matrix metalloproteinases (matrix metalloproteinases 2: P < 0.05; matrix metalloproteinases 3: P < 0.05) and the increase of tissue inhibitor of matrix metalloproteinases-2 in liver tissue in the Si group. Moreover, results of immunohistochemistry levels confirmed that at 240 min pro-inflammatory factors (tumor necrosis factor-α: P < 0.05; MCR1: P < 0.05) and matrix metalloproteinases ( matrix metalloproteinases 2: P < 0.05; matrix metalloproteinases 3: P < 0.05) had a statistically significantly lower expression in the Si group while tissue inhibitor of matrix metalloproteinases-2 had a higher expression. Conclusions Silibinin may have a beneficial effect on the protection of the liver.

1998 ◽  
Vol 85 (6) ◽  
pp. 2005-2011 ◽  
Author(s):  
Pavel L. Khimenko ◽  
G. J. Bagby ◽  
J. Fuseler ◽  
Aubrey E. Taylor

The effects of both recombinant rat tumor necrosis factor-α (TNF-α) and an anti-TNF-α antibody were studied in isolated buffer-perfused rat lungs subjected to either 45 min of nonventilated [ischemia-reperfusion (I/R)] or air-ventilated (V˙/R) ischemia followed by 90 min of reperfusion and ventilation. In the I/R group, the vascular permeability, as measured by the filtration coefficient ( K fc), increased three- and fivefold above baseline after 30 and 90 min of reperfusion, respectively ( P < 0.001). Over the same time intervals, the K fc for theV˙/R group increased five- and tenfold above baseline values, respectively ( P < 0.001). TNF-α measured in the perfusates of both ischemic models significantly increased after 30 min of reperfusion. Recombinant rat TNF-α (50,000 U), placed into perfusate after baseline measurements, produced no measurable change in microvascular permeability in control lungs perfused over the same time period (135 min), but I/R injury was significantly enhanced in the presence of TNF-α. An anti-TNF-α antibody (10 mg/rat) injected intraperitoneally into rats 2 h before the lung was isolated prevented the microvascular damage in lungs exposed to both I/R and V˙/R ( P < 0.001). These results indicate that TNF-α is an essential component at the cascade of events that cause lung endothelial injury in short-term I/R andV˙/R models of lung ischemia.


Cryobiology ◽  
2000 ◽  
Vol 41 (4) ◽  
pp. 301-314 ◽  
Author(s):  
Martina Lutterová ◽  
Zoltán Szatmáry ◽  
Marián Kukan ◽  
Daniel Kuba ◽  
Katarı́na Vajdová

2013 ◽  
Vol 39 (6) ◽  
pp. 795-800 ◽  
Author(s):  
Eun-Mi Rhim ◽  
Su-Jin Ahn ◽  
Ji-Yoen Kim ◽  
Kyung-Hee Kim ◽  
Hyeon-Woo Lee ◽  
...  

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