title: Effect of Khat on apoptosis and related gene Smac/DIABLO expression in the cerebral cortex of rats following transient focal ischemia.
abstract: BACKGROUND
  The leaves of the Khat shrub contain the major alkaloid compounds (cathinone) and cathine. These compounds can induce apoptosis and exacerbate the acute cerebral infarction, but the underlying mechanism is poorly understood. The present study aimed to investigate the effects of Khat treatment on the expression and cellular localization of Smac/Diablo (second mitochondrial activator of caspase) in the cortex of ischemic rat brain.
  
  
  METHODS
  Adult male Sprague-Dawley rats were administered Khat (3g/kg) twice daily for 4 weeks, then underwent left middle cerebral artery occlusion (MCAO) for 2h and reperfusion for 3, 6 and 12h, respectively. The infarction area was evaluated with 2,3,5-triphenyltetrazolium chloride (TTC) staining. Apoptosis was assessed by terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL). Smac/DIABLO expression levels in experimental and control groups were examined by immunohistochemistry and Western blot.
  
  
  RESULTS
  Khat significantly exacerbates the neurological damage compared with control (p<0.05). In addition, Khat-treatment significantly increased the number of TUNEL-positive cells 3h (p<0.01) and 12h (p<0.05) after reperfusion. Ischemia/reperfusion enhanced the release of Smac/DIABLO from the mitochondria to the cytosol after reperfusion. Such release of Smac/DIABLO was elevated after the rats were pretreated with Khat.
  
  
  CONCLUSIONS
  Our results indicate that Khat treatment can induce apoptosis through enhancing the release of Smac/DIABLO from the mitochondria to the cytosol after transient focal ischemia which may be an important mechanism of Khat neurotoxicity. Therefore, Khat chewing should be avoided by people who have cerebrovascular problems.
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
authors.forename: Walid A
authors.initials: WA
authors.lastname: Alsharafi
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
authors.forename: Fang-Fang
authors.initials: FF
authors.lastname: Bi
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Guangxi Traditional Chinese Medical University, Nanning, China.
authors.forename: Yue-Qiang
authors.initials: YQ
authors.lastname: Hu
authors.affiliation: Thamar Medical College, Thamar University, Yemen.
authors.forename: Hadi M
authors.initials: HM
authors.lastname: Mujlli
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China. Electronic address: xiaoboneuro@hotmail.com.
authors.forename: Bo
authors.initials: B
authors.lastname: Xiao
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins / Q000378:metabolism*; D029754:Catha; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002546:Ischemic Attack, Transient / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000378:metabolism*; D018515:Plant Leaves; D028321:Plant Preparations / Q000494:pharmacology*; D017207:Rats, Sprague-Dawley
chemical_list: D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins; C489013:DIABLO protein, rat; D024101:Mitochondrial Proteins; D028321:Plant Preparations
keywords: Apoptosis; Ischemia/reperfusion; Khat; Mitochondria; Smac/DIABLO