Abstract
ABSTRACTPurpose:The protective effect of silibinin on kidney and lung parenchyma during hepatic ischemia/reperfusion injury (IRI) is explored.Methods:Sixty-three Wistar rats were separated into three groups: sham; control (45 min IRI); and silibinin (200 μL silibinin administration after 45 min of ischemia and before reperfusion). Immunohistochemistry and real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) were used to evaluate the expression levels of MMP2, MMP3, MMP9, and TIMP2 on kidney and lung.Results:Comparing sham vs. control groups, confirmed that hepatic IRI increased both renal and lung MMP2, MMP3, MMP9 and TIMP2 expressions starting at 180 min (p<0.001). Comparison of the control vs. silibinin groups showed a statistically significant decrease in the expression levels of MMP2, MMP3, and MMP9 and increase of TIMP2 in kidney and lung parenchyma. The starting point of this decrease was at 120 min after reperfusion, both for kidney and lung parameters, and it was statistically significant at 240 min (p<0.001) for kidney, while silibinin showed a peak of lung protection at 180 min after hepatic reperfusion (p<0.001).Conclusions:Hepatic IRI causes distant kidney and lung damage, while a statistically significant protective action, both on kidney and lung parenchyma, is conveyed by the intravenous administration of silibinin.
Highlights
In liver surgery, clinical situations exist in which periods of ischemia are required, such as during trauma, removal of liver tumors, vascular reconstruction, and transplantation[1,2,3]
The difference in the expression of MMP2 in kidney between C and silibinin group (Si) groups was not significant at 120 and 180 min, but a significantly lower expression was found for the Si group at 240 min (Fig. 1a,b; Fig. 2a; Table 2)
Animals of Si group have a significantly lower expression of kidney MMP3 at 240 min and higher ΔCt value compared to the C group animals (Fig. 5b)
Summary
Clinical situations exist in which periods of ischemia are required, such as during trauma, removal of liver tumors, vascular reconstruction, and transplantation[1,2,3]. One of the most common, time honored, blood inflow control manipulations is the Pringle maneuver, which is performed by clamping the hepatic pedicle, thereby occluding both portal vein and hepatic artery[4] This process results in severe liver injury and disfunction[5,6,7,8,9], making ischemia reperfusion injury a major cause of morbidity and mortality in liver resection and liver transplantation surgery[10,11]. The first step seems to be portal hypertension due to portal pedicle occlusion This induces splanchnic vasodilation followed by intrarenal vasoconstriction[16,17,18], that causes activation of the renin-angiotensin-aldosterone axis[12,19]. Kidney injury worsens by the activation of pro-inflammatory cytokines (TNF-a, IL-6, IL-1), that drive renal parenchyma to appear significant inflammatory response
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