Effect of antituberculosis drug pyrazinamide on neuronal activity

doi:10.19871/j.cnki.xfcrbzz.2023.03.003

Abstract

Abstract: Objective Previous study suggests that pyrazinamide (PZA), a common anti-tuberculosis drug, may lead to neuronal damage. The mechanism of neuronal damage caused by PZA remains unclear. To further investigate the potential mechanism of neuronal damage caused by PZA , We constructed an in vitro model to study the effect of PZA on neurons. Method The in-vitro neuron model were constructed, which were incubated with different concentrations of PZA for 6h. Optimal concentration of PZA was selected. Based on optimal concentration, the neurons were then incubated with PZA (10µmol/L) for 12h (10-PZA-12h), and the neurons were incubated with PZA(10µmol/L) for 6h and then replaced with normal medium for another 6h (10-PZA-normal-6h). We observed the structure and morphology of neurons and detected the ATP content, survival rate, expression of Na⁺/K⁺-ATPase α1 subunit(ATP1A1), electrophysiology—resting potential (RP) and action potential (AP) in neurons. Result After the neurons were incubated in PZA (10µmol/L) for 6h, the neuronal structure, morphology and survival rate were not significantly changed, but the ATP content, the expression of ATP1A1 and amplitude of AP were decreased. Inversely, the RP was increased. In 10-PZA-12h group, the morphology and structure of neurons were changed; the ATP content, neuronal survival rate, the expression of ATP1A1 and amplitude of AP were significantly decreased; the RP was increased. In 10-PZA-normal-6h group,the neuronal morphology and structure, ATP content, survival rate, the expression of ATP1A1 and amplitude of AP and RP were not significantly changed. Conclusion PZA inhibits the activity of neurons. With the extension of drug action time, the neurons appear damage,and timely removal of inducement can save neurons.

Key words: Antituberculosis drugs, Pyrazinamide, Neuron, Adenosine triphosphate, Electrophysiology

CLC Number:

Shao Honghua, Zhu Qingdong, Long Qian, Luo Xiaolu, Nong Jianhong, Li Sijun, Wu Fengyao. Effect of antituberculosis drug pyrazinamide on neuronal activity[J]. Electronic Journal of Emerging Infectious Diseases, 2023, 8(3): 12-18.

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