pregabalin and Glioblastoma

As a member of the platinum drug group, oxaliplatin (OXAL) is used to treat brain tumors, although its use is limited through excessive calcium ion (Ca) influx and reactive oxygen species (ROS) production in neurons. The Ca permeable transient receptor potential vanilloid 1 (TRPV1) channel is activated by ROS, and its activity might be reduced by the antioxidant property of pregabalin (PREGAB). This study aimed to investigate the protective action of PREGAB against OXAL-induced oxidative neurotoxicity in human glioblastoma (DBTRG) cells. The DBTRG cells were divided into four treatment groups: control, PREGAB (500 µM for 1 h), OXAL (25 µM for 24 h), and PREGAB + OXAL. In the laser confocal microscope and plate reader analyses, apoptosis, mitochondrial membrane depolarization (JC-1), cell death (propidium iodide/Hoechst rate), and ROS-level production increased by activating TRPV1 in the cells using the OXAL treatment, although the cell viability values decreased. However, these values were recovered in the PREGAB + OXAL group using PREGAB and TRPV1 inhibitor (capsazepine) treatments. In the patch-clamp analyses, OXAL-induced TRPV1 channel activation in the OXAL group also decreased in the PREGAB + OXAL group using the PREGAB and capsazepine treatments. In conclusion, the apoptosis and oxidant actions of OXAL were increased by activation of the TRPV1 channel, but this effect was diminished by the PREGAB treatment. PREGAB treatment has the potential to be an effective strategy in the treatment of OXAL-induced oxidative neurotoxicity.

Topics: Apoptosis; Brain Neoplasms; Calcium; Caspase 3; Caspase 9; Cell Line, Tumor; Drug Interactions; Glioblastoma; Humans; Neurons; Neurotoxicity Syndromes; Oxaliplatin; Oxidative Stress; Patch-Clamp Techniques; Pregabalin; Reactive Oxygen Species; TRPV Cation Channels

Gabapentin (GBP) and pregabalin (PGB) exert antinociceptive effects on chronic nociceptive responses with neuropathic or inflammatory conditions. Furthermore, it is considered that GBP and PGB exhibit anti‑inflammatory effects by modulating the substance P (SP)‑mediated neurokinin‑1 receptor (NK1R; a SP receptor) response. Thus, in the present study, the effects of GBP and PGB on SP‑induced activation were investigated in the human glioblastoma astrocytoma U373 MG cell line, which expresses high levels of functional high‑affinity NK1R, and produces interleukin (IL)‑6 and IL‑8 in response to SP. The results indicated that GBP and PGB suppressed the SP‑induced production of IL‑6, and IL‑8 in U373 MG cells. Furthermore, GBP and PGB inhibited the SP‑induced phosphorylation of p38 mitogen‑activated protein kinase (MAPK) and nuclear factor (NF)‑κB, and the nuclear translocation of NF‑κB in U373 MG cells. Together, these observations suggest that GBP and PGB likely prevent SP‑induced IL‑6 and IL‑8 production in U373 MG cells via the inhibition of signaling molecules, including p38 MAPK and NF‑κB, thereby exhibiting antineuroinflammatory effects.

Topics: Amines; Anti-Inflammatory Agents; Astrocytoma; Cell Line, Tumor; Cyclohexanecarboxylic Acids; Gabapentin; gamma-Aminobutyric Acid; Glioblastoma; Humans; Interleukin-6; Interleukin-8; MAP Kinase Signaling System; NF-kappa B; p38 Mitogen-Activated Protein Kinases; Phosphorylation; Pregabalin; Receptors, Neurokinin-1; Substance P

Topics: Anticonvulsants; Botulinum Toxins, Type A; Epilepsia Partialis Continua; Fructose; gamma-Aminobutyric Acid; Glioblastoma; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Pain; Pregabalin; Radionuclide Imaging; Supratentorial Neoplasms; Topiramate