Ukr.Biochem.J. 2019; Volume 91, Issue 5, Sep-Oct, pp. 16-24

doi: https://doi.org/10.15407/ubj91.05.016

Agonists of CB1 and NMDA receptors decrease the toxic effect of organophosphorus compound paraoxon on PC12 cells

F. Salem1, F. Bahrami1,2, Z. Bahari2, Z. Jangravi3, S. Najafizadeh-Sari4

1Neuroscience Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran;
2Department of Physiology and Medical Physics, Faculty of Medicine, Baqiyatallah University of Medical Sciences, Tehran, Iran;
3Departmentof Biochemistry, Faculty of Medicine, Baqiyatallah University
of Medical Sciences, Tehran, Iran;
4Student’ Research Committee (SRC), Baqiyatallah University of Medical Sciences, Tehran, Iran;
e-mail: f.bahrami@bmsu.ac.ir or farideh_bahrami@yahoo.com

Received: 01 July 2019; Accepted: 13 August 2019

Pharmacological studies allow to suggest that activation of cannabinoid type 1 receptors (CB1) have a neuroprotective role against toxicity induced by organophosphate agents, but the exact mechanisms of this effect as well as interaction with receptors of other types are far from clear. Therefore, the aim of current study was to evaluate the effect of CB1 and NMDA receptors agonists on cell viability and biomarkers of oxidative stress and lipid peroxidation in PC12 cells exposed to paraoxon. PC12 cells were exposed to 100 µm paraoxon as organophosphate agent. Treatments with 1 µM arachidonyl-2′-chloroethylamide (ACEA) as specific agonist of CB1 receptors, 100 µM N-methyl-D-aspartate (NMDA) as agonist of NMDA receptors and 1 µM AM251 as antagonist of CB1 receptors were done. Cell via­bility and biomarkers of oxidative stress were evaluated after 48 h of incubation. The level of CB1 receptor protein was evaluated by Western blotting. It was demonstrated that PC12 cells treatment with paraoxon led to cell viability inhibition, glutathione level, superoxide dismutase and catalase activity reduction, lipid peroxidation intensification and CB1 receptor expression attenuation. Application of ACEA and NMDA was shown to be followed by normalization of these indices. The protective effect of ACEA was abolished when the CB1 receptors antagonist AM251 was applied. The study revealed that application of ACEA and NMDA can protect PC12 cells against paraoxon induced toxicity through antioxidant capacity increment, lipid peroxidation inhibition and enhanced expression of CB1 receptors.

Keywords: , , , , , ,


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