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.
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