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

Pharmacol Biochem Behav. 2013 Nov 15:113:53-62. doi: 10.1016/j.pbb.2013.10.008. Epub 2013 Oct 18.

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.

Keywords: 2,2-diphenyl-1-picrylhydrazyl; 2,3,5-triphenyltetrazolium chloride; 5,5′-dithiobis-2-nitrobenzoic acid; 6-OHDA; 6-hydroxydopamine; ANOVA; ATP; Adenosine triphosphate; Analysis of variance; Apaf-1; Apoptotic protease activating factor-1; B-cell lymphoma-2; BSA; Bax; Bcl-2; Bcl-2 associated X protein; Behavior; Body weight; Bovine serum albumin; CBF; CV; Caspase; Cerebral blood flow; Cysteine-aspartic proteases; DPPH; DTNB; ECA; EDTA; External carotid artery; FT; Flexion Test; GSH; H & E; Hematoxylin and eosin; I/R; ICA; Internal carotid artery; Ischemia–reperfusion; LPO; Lipid peroxidation; MCA; MCAO; Middle cerebral artery; Middle cerebral artery occlusion; PBS; PMS; Pi; Post mitochondrial supernatant; ROS; Reactive oxygen species; S-1; SMA; SOD; Spontaneous Motor Activity; Supernatant-1; Superoxide dismutase; TBA; TBARS; TCA; TTC; b.wt; caspase; cresyl violet; ethylene diamine tetra-acetic acid; iPCD; inorganic phosphate; intrinsic Programmed cell death; phosphate buffer saline; reduced glutathione; thiobarbituric acid; thiobarbituric reactive substances; trichloroacetic acid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Behavior, Animal / drug effects*
  • Brain Ischemia / metabolism
  • Brain Ischemia / pathology
  • Brain Ischemia / physiopathology*
  • Enzyme-Linked Immunosorbent Assay
  • Guaiacol / administration & dosage
  • Guaiacol / analogs & derivatives*
  • Guaiacol / pharmacology
  • Male
  • Oxidative Stress / drug effects*
  • Rats
  • Rats, Wistar

Substances

  • zingerone
  • Guaiacol