Delayed administration of zingerone mitigates the behavioral and histological alteration via repression of oxidative stress and intrinsic programmed cell death in focal transient ischemic rats

Kumar Vaibhav, Pallavi Shrivastava, Rizwana Tabassum, Andleeb Khan, Hayate Javed, Md Ejaz Ahmed, Farah Islam, Mohammed M. Safhi, Fakhrul Islam

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

The neuronal mitochondria succumb to ischemia-reperfusion injury and release huge amount of reactive oxygen species and ultimately lead the neurons to intrinsic pathway of programmed cell death (iPCD). The present study was undertaken to elucidate the ischemia-reperfusion-induced oxidative stress and molecular events in iPCD 24 h post ischemia-reperfusion injury and plausible mitigation by zingerone, a potent antioxidant of ginger rhizome. The right middle cerebral artery was occluded for 2 h followed by reperfusion for 22 hours. A maximum infarct volume (43.29%) and mitochondrial injury (56.99%) was observed in middle cerebral artery occlusion (MCAO) group. However, zingerone administration (50 and 100 mg/kg b.wt. orally twice) at 5 h and 12 h from initiation of MCAO showed a significant reduction in infarct volume and mitochondrial injury (p < 0.001). Zingerone treatment significantly improved behavioral outputs (p < 0.05) and histological architecture (p < 0.001) by reducing lipid peroxidation (p < 0.01), augmenting the reduced glutathione content (p < 0.01) and restoring Na+-K+ ATPase and superoxide dismutase activities (p < 0.01) in MCAO brain. Zingerone successfully reduced the caspase-3 and -9 activities in MCAO group (p < 0.05) and succeeded in lowering the expressions of pro-apoptotic proteins - Apaf-1 and Bax (p < 0.001). The present study suggests that zingerone is a potent antioxidant that salvaged the ischemic penumbral zone neurons by inhibiting iPCD and oxidative stress.

Original languageEnglish (US)
Pages (from-to)53-62
Number of pages10
JournalPharmacology Biochemistry and Behavior
Volume113
DOIs
StatePublished - Nov 12 2013

Keywords

  • Apaf-1
  • Bax
  • Bcl-2
  • Behavior
  • Caspase
  • Ischemia-reperfusion

ASJC Scopus subject areas

  • Biochemistry
  • Toxicology
  • Pharmacology
  • Clinical Biochemistry
  • Biological Psychiatry
  • Behavioral Neuroscience

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