Levetiracetam modulates hypoxia-induced inflammation and oxidative stress via inhibition of TRPV1 channel in the DBTRG glioblastoma cell line

Abstract

Hypoxia (HPX) induces mitochondrial oxidative stress, inflammation and apoptosis in brain and neurons. Ca2+ permeable TRPV1 channel is gated by capsaicin and reactive oxygen species (ROS), although its activity was decreased in neurons by antioxidants. LEV has been used as antiepileptic drug in the treatment of epilepsy. LEV inhibited voltage gated calcium channels via its antioxidant property in neurons. Hence, it may modulate HPX-induced ROS, inflammation and apoptosis via inhibition of TRPV1 in the DBTRG cells. The DBTRG glioblastoma cells were divided into four groups as control, LEV (100 µM and 24 hours), and HPX and LEV+HPX. HPX in the cells was induced by using CoCl2 (200 µM and 24 hours). HPX-induced intracellular Ca2+ response to TRPV1 activation was increased in the cells from capsaicin, although it was reduced by the LEV and TRPV1 blocker (capsazepine). LEV treatment improved intracellular Ca2+ responses, mitochondrial function, suppressed the generation of cytokine (IL-1β, and TNF-α) and ROS in the cells. Apoptosis, lipid peroxidation level, caspase -3 and -9 activities were increased in the cells exposed to the HPX, although glutathione peroxidase activity and reduced glutathione level were decreased by the HPX. However, they were modulated in the cells by LEV treatment. In DBTRG neuronal cells exposed to HPX conditions, the neuroprotective effects of LEV were shown to be exerted via modulation of oxidative stress, inflammation, apoptosis and TRPV1 channel. LEV could be used as an effective agent via modulation of TRPV1 in the treatment of neurodegeneration exposure to HPX.

Keywords

• Apoptosis,Hypoxia,Inflammation,Levetiracetam,Oxidative stress,TRPV1 channel

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