Pro-inflammatory cytokines/chemokines, TNF-α, IL-6 and MCP-1, as biomarkers for the nephro- and pneumoprotective effect of silibinin after hepatic ischemia/reperfusion: Confirmation by immunohistochemistry and qRT-PCR

Basic Clin Pharmacol Toxicol. 2022 Apr;130(4):457-467. doi: 10.1111/bcpt.13704. Epub 2022 Jan 26.

Abstract

The present study investigated the potential nephro- and pneumoprotective effect of silibinin (Si) after hepatic ischemia-reperfusion (I/R) injury, by measuring pro-inflammatory factors. Sixty-three rats were randomly assigned into three groups, as follows: (a) the sham group (n = 7 rats), subjected to opening and closing the abdomen; (b) the control group (n = 28 rats), subjected to 45-min hepatic ischemia followed by reperfusion; and (c) the silibinin group (n = 28), subjected to 45-min hepatic ischemia followed by intravenous administration of lyophilised SLB-HP-β-CD before reperfusion. Control and silibinin groups were further subdivided into time-point groups, according to the duration of reperfusion. TNF-α, IL-6 and MCP-1 expressions were determined immunohistochemically and by qrT-PCR at each time-point. Kidney TNF-α expression was significantly lower at 180 and 240 min, while lung TNF-α expression was significantly lower at 240 min. Comparison between the control and Si group at the same time-points showed very strong evidence of difference at 240 min, with the levels of IL-6 shifting towards lower values in the Si group. Finally, we found a high MCP-1 expression after 120 min. We conclude that hepatic I/R injury remotely increases pro-inflammatory mediators in the kidney and lung, whereas silibinin shows a time-dependent nephro- and pneumoprotective effect.

Keywords: hepatic ischemia-reperfusion injury; kidney; lung; pro-inflammatory mediators; silibinin.

MeSH terms

  • Animals
  • Biomarkers / metabolism
  • Cytokines / metabolism
  • Immunohistochemistry
  • Interleukin-6 / metabolism
  • Ischemia / metabolism
  • Liver
  • Rats
  • Rats, Wistar
  • Reperfusion
  • Reperfusion Injury* / drug therapy
  • Reperfusion Injury* / metabolism
  • Reperfusion Injury* / prevention & control
  • Reverse Transcriptase Polymerase Chain Reaction
  • Silybin / metabolism
  • Silybin / pharmacology
  • Tumor Necrosis Factor-alpha* / genetics
  • Tumor Necrosis Factor-alpha* / metabolism

Substances

  • Biomarkers
  • Cytokines
  • Interleukin-6
  • Tumor Necrosis Factor-alpha
  • Silybin