Effect of silibinin on the expression of MMP2, MMP3, MMP9 and TIMP2 in kidney and lung after hepatic ischemia/reperfusion injury in an experimental rat model

Acta Cir Bras. 2021 Nov 8;36(9):e360904. doi: 10.1590/ACB360904. eCollection 2021.

Abstract

Purpose: 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.

MeSH terms

  • Animals
  • Ischemia
  • Kidney
  • Liver Diseases
  • Lung
  • Matrix Metalloproteinase 2*
  • Matrix Metalloproteinase 3
  • Matrix Metalloproteinase 9
  • Rats
  • Rats, Wistar
  • Reperfusion Injury* / drug therapy
  • Reperfusion Injury* / prevention & control
  • Silybin
  • Tissue Inhibitor of Metalloproteinase-2

Substances

  • Timp2 protein, rat
  • Tissue Inhibitor of Metalloproteinase-2
  • Silybin
  • Matrix Metalloproteinase 3
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9