Geraniol activates Nrf-2/HO-1 signaling pathway mediating protection against oxidative stress-induced apoptosis in hepatic ischemia-reperfusion injury

Naunyn Schmiedebergs Arch Pharmacol. 2020 Oct;393(10):1849-1858. doi: 10.1007/s00210-020-01887-1. Epub 2020 May 16.

Abstract

Geraniol (GOH) is a natural essential oil that possesses antioxidant, anti-inflammatory, and antiapoptotic properties by various signaling pathways. Liver ischemia-reperfusion injury (IRI) is a serious event that triggers liver dysfunction or even failure. Nuclear factor erythroid 2-related factor 2 (Nrf2), a transcriptional factor, maintains cellular defense mechanism through antioxidant and anti-inflammatory properties. To detect GOH effect against liver IRI through the activation of the Nrf2/HO-1 antioxidant pathway, five groups of rats were randomized to normal, sham, IR, GOH, and GOH/IR. Blood samples and liver tissues were collected to measure various biochemical parameters related to liver function, and oxidative stress as well as inflammatory and apoptotic indicators besides liver tissue histopathology was evaluated by light microscopy. GOH induces activation of Nrf2 along with the upregulation of HO-1 expression. Also, the antioxidant activity of GOH was shown by the elevation of total antioxidant capacity and GSH levels, together with normalizing malondialdehyde. Regarding the anti-inflammatory effect of GOH, it suppresses the levels of TNF-α, iNOS, and COX-2. Additionally, the antiapoptotic effect of GOH, Bax, and caspase-3, 9 were reduced in liver tissue. GOH is a promising hepatoprotective agent in liver IRI through the activation of Nrf2/HO-1 antioxidant pathway.

Keywords: Caspase-3; Cyclooxygenase-2; Geraniol; Inducible nitric oxide synthase; Liver ischemia-reperfusion; Nrf2/HO-1 antioxidant pathway.

MeSH terms

  • Acyclic Monoterpenes / pharmacology
  • Acyclic Monoterpenes / therapeutic use*
  • Animals
  • Apoptosis / drug effects
  • Apoptosis / physiology
  • Heme Oxygenase (Decyclizing) / metabolism*
  • Liver / drug effects
  • Liver / metabolism*
  • Liver / pathology
  • Male
  • NF-E2-Related Factor 2 / metabolism*
  • Oxidative Stress / drug effects*
  • Oxidative Stress / physiology
  • Rats
  • Rats, Sprague-Dawley
  • Reperfusion Injury / metabolism*
  • Reperfusion Injury / pathology
  • Reperfusion Injury / prevention & control
  • Signal Transduction / drug effects
  • Signal Transduction / physiology

Substances

  • Acyclic Monoterpenes
  • NF-E2-Related Factor 2
  • Nfe2l2 protein, rat
  • Heme Oxygenase (Decyclizing)
  • Hmox1 protein, rat
  • geraniol