The possible protective effect of colchicine against liver damage induced by renal ischemia-reperfusion injury: role of Nrf2 and NLRP3 inflammasome

Can J Physiol Pharmacol. 2020 Dec;98(12):849-854. doi: 10.1139/cjpp-2020-0230. Epub 2020 Jul 8.

Abstract

Ischemia-reperfusion injury (IRI) induces an inflammatory response and production of reactive oxygen species, which affects the organs remote to the sites of renal IR. However, remote effects of renal IRI on the liver need further investigations. Renal injury associated with liver disease is a common clinical problem. Colchicine is an established drug for microtubule stabilization that may reduce tissue injury and has antioxidant and antiinflammatory effects. The aim of the present study was (i) to assess the hepatic changes after induction of renal IRI, (ii) to explore the possible protective effect of colchicine on liver injury following renal IRI, and (iii) to investigate the possible mechanisms underlying the potential effect. Forty rats were randomly divided into four groups: sham operation group, colchicine-treated group, IR group, and colchicine-treated IR group. Colchicine treatment improved liver function (ALT/AST) after renal IRI, decreased hepatic oxidative stress and cell apoptosis by reducing hepatic MDA, upregulating hepatic total antioxidant capacity, Nrf2, and HO-1. Furthermore, colchicine inhibited inflammatory responses by downregulating hepatic NLRP3 inflammasome, IL-1β, and caspase-1. Colchicine attenuates renal IRI-induced liver injury in rats. This effect may be due to reducing inflammation and oxidative stress markers.

Keywords: Nrf2; colchicine; foie; ischémie-reperfusion rénale; liver; renal ischemia–reperfusion.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Caspase 1 / metabolism
  • Colchicine / pharmacology*
  • Cytoprotection / drug effects
  • Inflammasomes / metabolism*
  • Kidney / drug effects*
  • Kidney / injuries
  • Liver / drug effects*
  • Liver / pathology
  • NF-E2-Related Factor 2 / metabolism*
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism*
  • Oxidative Stress / drug effects
  • Rats
  • Reactive Oxygen Species / metabolism
  • Reperfusion Injury / metabolism
  • Reperfusion Injury / pathology*

Substances

  • Inflammasomes
  • NF-E2-Related Factor 2
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Reactive Oxygen Species
  • Caspase 1
  • Colchicine