Adiponectin attenuates NADPH oxidase-mediated oxidative stress and neuronal damage induced by cerebral ischemia-reperfusion injury

Biochim Biophys Acta Mol Basis Dis. 2017 Dec;1863(12):3265-3276. doi: 10.1016/j.bbadis.2017.08.010. Epub 2017 Aug 24.

Abstract

Adiponectin (APN), which is a major adipokine that regulated glucose and lipid metabolism, plays an important role in the protection of the cerebral nervous system. It also has been suggested to have anti-inflammatory effects and ameliorate oxidative stress. Stroke is a universal cause of death and permanent disability. Ischemic stroke accounts for most cases of stroke, and is characterized by cerebral ischemia and neurological deficits. We aimed to investigate the effects of APN-peptide (APN-P) in neurons following ischemia reperfusion (I/R) in C57BL/6J mice, and to study the potential mechanisms underlying its effects. Mice were treated with vehicle, 2.5, 5, or 10mg/kg of APN-P and 2.5mg/kg of apocynin or vehicle before middle cerebral artery occlusion. Neurological deficits, infarct size, neuronal injury, and the ultrastructure of neurons were assessed. In addition, the levels of reactive oxygen species, superoxide dismutase, and malondialdehyde were measured. We assessed neuronal apoptosis using terminal deoxynucleotidyl transferase dUTP nick end labeling. The levels of oxidative stress- and apoptosis-related proteins were measured by western blot. Our results suggest that APN-P at 5mg/kg markedly improved neurological deficits, decreased infarct size, and attenuated neuronal injury after cerebral I/R injury. APN-P treatment also decreased neuronal apoptosis. Additionally, the increased levels of oxidative stress- and apoptosis-related proteins levels following I/R were alleviated by APN-P treatment. In conclusion, APN-P inhibits neuronal apoptosis and alleviates oxidative stress in neurons subjected to I/R, suggesting that it may be beneficial for the treatment of brain damage following ischemic stroke.

Keywords: Adiponectin; Cerebral ischemia-reperfusion injury; Oxidative stress; Stroke.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetophenones / pharmacology
  • Adiponectin / metabolism
  • Adiponectin / pharmacology*
  • Animals
  • Apoptosis / drug effects
  • Brain Ischemia / drug therapy
  • Brain Ischemia / enzymology
  • Brain Ischemia / pathology
  • DNA Nucleotidylexotransferase / metabolism
  • Disease Models, Animal
  • Male
  • Mice
  • Mice, Inbred C57BL
  • NADPH Oxidases / metabolism*
  • Neurons / drug effects*
  • Neurons / enzymology
  • Neurons / metabolism*
  • Neurons / pathology
  • Oxidative Stress / drug effects*
  • Reactive Oxygen Species / metabolism
  • Reperfusion Injury / drug therapy*
  • Reperfusion Injury / enzymology
  • Reperfusion Injury / pathology
  • Stroke / drug therapy
  • Stroke / enzymology
  • Stroke / pathology
  • Superoxide Dismutase / metabolism

Substances

  • Acetophenones
  • Adiponectin
  • Adipoq protein, mouse
  • Reactive Oxygen Species
  • acetovanillone
  • Superoxide Dismutase
  • NADPH Oxidases
  • DNA Nucleotidylexotransferase