Vagus nerve stimulation protects against acute liver injury induced by renal ischemia reperfusion via antioxidant stress and anti-inflammation

Biomed Pharmacother. 2019 Sep:117:109062. doi: 10.1016/j.biopha.2019.109062. Epub 2019 Jun 6.

Abstract

Objective: Renal ischemia reperfusion (I/R) is not an isolated event; however, it results in remote organ dysfunction. Vagus nerve stimulation (VNS) has shown protective effects against renal I/R injury via an anti-inflammatory mechanism. This study aimed to investigate whether VNS could attenuate liver injury induced by renal I/R and identify the underlying mechanisms.

Methods: Eighteen healthy male Sprague-Dawley rats (200-250 g) were equally divided into three groups: sham group (sham surgery without I/R or VNS), I/R group (renal I/R) and VNS group (renal I/R plus VNS). The I/R model was established by excising the right kidney and then clamping the left renal pedicle with an occlusive nontraumatic microaneurysm clamp for 45 min followed by a 6-h reperfusion. The rats in the VNS group received spontaneous left cervical VNS with renal ischemia and reperfusion. At the end of the experiment, blood and liver tissues were collected to detect liver function, oxidative stress and inflammatory parameters. Additionally, TUNEL staining, real-time PCR, western blotting and hematoxylin and eosin staining of liver tissues were performed to assess liver injury and the underlying mechanisms.

Results: Kidney and liver function was severely damaged in the I/R group compared to the sham group. However, VNS significantly protected kidney and liver function. Rats treated with VNS revealed decreases in oxidative enzymes, apoptosis and levels of tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) in serum and liver compared with rats in the I/R group. Rats in the VNS group also showed increased antioxidant stress responses compared to rats in the I/R group.

Conclusion: VNS exerts protective effects against liver injury from renal I/R via inhibiting oxidative stress and apoptosis, downregulating inflammatory cytokines and enhancing antioxidative capability in the liver, and may become a promising adjuvant therapeutic strategy for treating liver injury induced by acute renal injury.

Keywords: Inflammation; Liver injury; Organ crosstalk; Renal ischemia reperfusion injury; vagus nerve stimulation.

MeSH terms

  • Acute Disease
  • Animals
  • Anti-Inflammatory Agents / therapeutic use*
  • Antioxidants / therapeutic use*
  • Apoptosis
  • Cytokines / blood
  • Hepatocytes / metabolism
  • Hepatocytes / pathology
  • Inflammation Mediators / blood
  • Kidney / blood supply*
  • Kidney / pathology
  • Kidney / physiopathology
  • Liver / enzymology
  • Liver / injuries*
  • Liver / pathology
  • Liver / physiopathology
  • Male
  • Oxidation-Reduction
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats, Sprague-Dawley
  • Reperfusion Injury / blood
  • Reperfusion Injury / complications*
  • Reperfusion Injury / drug therapy*
  • Vagus Nerve Stimulation*
  • bcl-2-Associated X Protein / genetics
  • bcl-2-Associated X Protein / metabolism

Substances

  • Anti-Inflammatory Agents
  • Antioxidants
  • Cytokines
  • Inflammation Mediators
  • RNA, Messenger
  • bcl-2-Associated X Protein