Abstract
BackgroundGlutathione S-transferases (GSTs) play an important role in metabolizing anti-epileptic drugs (AEDs) in liver. Expressions of GSTs in brain, which may result in poor efficacy of AEDs, have not been well studied. Using clinical cortex specimen from 32 intractable epileptic subjects and 8 non-epileptic controls, the present study investigated the correlation between GSTs and intractable epilepsy.ResultsThree different GST isoforms (α, μ, and π) were detected with immunohistochemistry. GST-α expression was not seen in any cortex specimens. Sixty three percent (63%) of control and 53% of intractible epileptic specimens showed GST-μ immunoreactivity. No significant difference in intensity of GST-μ staining was observed between these two groups. GST-π expression was found in endothelial cells and glial cells/astrocytes. Fifty percent (50%) of the control patients and 66% of the epileptic patients were GST-π positive. The grading of epileptic patients was significantly higher than that of control patients (p < 0.01).ConclusionHigh levels of GST-π in endothelial cells and glial cells/astrocyte correlate to medical intractable epilepsy, suggesting that GST-π contributes to resistance to AED treatment.
Highlights
Glutathione S-transferases (GSTs) play an important role in metabolizing antiepileptic drugs (AEDs) in liver
The majority of epileptic patients are successfully treated with antiepileptic drugs (AEDs)
AEDs can prevent abnormal neuronal firing and seizure spread at seizure focus
Summary
Glutathione S-transferases (GSTs) play an important role in metabolizing antiepileptic drugs (AEDs) in liver. Expressions of GSTs in brain, which may result in poor efficacy of AEDs, have not been well studied. Using clinical cortex specimen from 32 intractable epileptic subjects and 8 non-epileptic controls, the present study investigated the correlation between GSTs and intractable epilepsy. The majority of epileptic patients are successfully treated with antiepileptic drugs (AEDs). About 20–25% of epileptic patients, as defined as medically intractable epilepsy, fail to respond to AEDs [2]. The enzymatic activity of Glutathione S-transferases (GSTs) in liver plays an essential role in metabolizing and clearing AEDs [3,4,5]. GSTs are widely expressed in almost every tissue, while some isoforms show tissue-specific distribution. Expression of GST-α, μ, and π in CNS was reported [9,10,11,12]
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