A deuterohemin peptide protects cerebral ischemia-reperfusion injury by preventing oxidative stress in vitro and in vivo

Exp Cell Res. 2023 Jan 1;422(1):113432. doi: 10.1016/j.yexcr.2022.113432. Epub 2022 Nov 25.

Abstract

Cerebral ischemia-reperfusion injury (CIRI) is a brain injury that usually occurs during thrombolytic therapy for acute ischemic stroke and impacts human health. Oxidative stress is one of the major causative factors of CIRI. DhHP-3 is a novel peroxidase-mimicking enzyme that exhibits robust reactive oxygen species (ROS) scavenging ability in vitro. Here, we established in vitro and in vivo models of cerebral ischemia-reperfusion to mechanistically investigate whether DhHP-3 can alleviate CIRI. DhHP-3 could reduce ROS, down-regulate apoptotic proteins, suppress p53 phosphorylation, attenuate the DNA damage response (DDR), and inhibit apoptosis in SH-SY5Y cells subjected to oxygen-glucose deprivation/re-oxygenation (OGD/R) and in the brain of Sprague Dawley rats subjected to transient middle cerebral artery occlusion. In conclusion, DhHP-3 has bioactivity of CIRI inhibition through suppression of the ROS-induced apoptosis.

Keywords: Apoptosis; Cerebral ischemia-reperfusion injury; ROS; p53.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Brain Ischemia* / metabolism
  • Humans
  • Ischemic Stroke*
  • Neuroblastoma*
  • Oxidative Stress
  • Peptides / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Reactive Oxygen Species / metabolism
  • Reperfusion Injury* / drug therapy
  • Reperfusion Injury* / genetics
  • Reperfusion Injury* / prevention & control

Substances

  • Reactive Oxygen Species
  • deuterohemin
  • Peptides