SS-31 Protects Liver from Ischemia-Reperfusion Injury via Modulating Macrophage Polarization

Longcheng Shang1, Haozhen Ren1,2, Shuai Wang1,2

  • 1Department of Hepatobiliary Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.

Insights

SS-31 peptide effectively protects the liver from ischemia-reperfusion injury (IRI) by reducing oxidative stress and inflammation. This novel antioxidant peptide targets mitochondria to suppress harmful reactive oxygen species (ROS) and regulate macrophage polarization, offering a promising clinical treatment for liver IRI.

Area of Science:

  • Hepatology
  • Immunology
  • Pharmacology

Background:

  • Ischemia-reperfusion injury (IRI) is a significant clinical challenge in liver surgery, often leading to substantial organ damage.
  • Oxidative stress and inflammatory responses are key contributors to liver injury during IRI.
  • Mitochondrial-targeted antioxidants represent a promising therapeutic strategy, yet the role of SS-31 in hepatic IRI remains unclear.

Purpose of the Study:

  • To investigate the protective effects of SS-31 against liver IRI.
  • To elucidate the underlying protective mechanisms of SS-31 in hepatic IRI.

Main Methods:

  • Assessment of liver injury using Hematoxylin and Eosin (HE) staining, serum ALT/AST levels, and TUNEL staining.
  • Evaluation of oxidative stress markers and inflammatory responses post-SS-31 treatment.
  • Analysis of SS-31's effect on reactive oxygen species (ROS) production and macrophage polarization (STAT1/STAT3 signaling).

Main Results:

  • SS-31 treatment significantly attenuated liver injury, as evidenced by improved histological scores, reduced ALT/AST levels, and decreased apoptosis.
  • SS-31 administration effectively suppressed oxidative stress and inflammatory markers.
  • SS-31 reduced ROS production and inhibited M1 polarization of macrophages by regulating STAT1/STAT3 signaling, leading to decreased pro-inflammatory cytokine release.

Conclusions:

  • SS-31 demonstrates significant protective effects against liver IRI.
  • SS-31 ameliorates liver injury by scavenging ROS and modulating macrophage polarization via the STAT1/STAT3 pathway.
  • SS-31 holds potential as a therapeutic agent for clinical treatment of liver IRI.