Kurkumin Yüksek Doz Morfinin Neden Olduğu Apoptozis ve Oksidatif Nörotoksisiteyi TRPV4 Katyon Kanalını Düzenleyerek Azaltır

Öz

Amaç: Nöropatik ağrıyı tedavi etmek için yüksek doz (H-MRP) ve uzun süreli morfin uygulanması kullanılır. Bununla birlikte, H-MRP tedavisi, morfin toleransı, aşırı reaktif oksijen türleri (ROS) üretimi, apoptozis ve Ca+2 akışının artmasına neden olur. Sinir hasarı nedeniyle zarar gören SH-SY5Y sinir hücrelerinde, kurkumin (CRC) TRPV4 katyon kanalını inhibe ederek ROS'un neden olduğu apoptozis artışını azaltır. H-MRP, SH-SY5Y hücrelerinde TRPV4 katyon kanalını inhibe ederek aşırı ROS ve apoptozis oluşumunu önlemek için CRC etkisi henüz araştırılmamıştır. Bu çalışmada, CRC tedavisinin TRPV4 kanalını düzenleyerek mitokondriyal ROS üretimini ve apoptozis oluşumunu H-MRP inkübasyonunu nasıl etkilediğini SH-SY5Y hücrelerinde araştırıldı. Materyal ve Metot: SH-SY5Y hücrelerinde dört ana grup oluşturuldu. Bunlar; kontrol, normal morfin (N-MRP) (50 µM ve 24 saat), H-MRP (500 µM ve 24 saat) ve H-MRP + CRC (5 µM ve 24 saat). Bulgular: TRPV4 agonisti (GSK1016790A) ile inkübasyon, ROS, mitokondriyal fonksiyon bozukluğu, debris (ölü hücre artığı), apoptosis, kaspaz -3, kaspaz -8, kaspaz -9 ve lipit peroksidasyon düzeylerini artırdı. Bununla birlikte, TRPV4 antagonisti (rutenyum kırmızısı) ve CRC inkübasyonları bu artışları azalttı. Rutenyum kırmızısı ve CRC inkübasyonları, H-MRP inkübasyonunun neden olduğu hücre canlılığı yüzdesi, canlı hücre sayısı, glutatyon ve glutatyon peroksidaz düzeyleri azalışlarını artırdı. Sonuç: CRC tedavisi, TRPV4 kanalını baskılayarak H-MRP'nin mitokondriyal oksidan ve sinir hücre ölümü etkilerini azalttı. H-MRP neden olduğu mitokondriyal oksidatif stres ve sinir hücre harabiyetini önlemek için CRC tedavisi alternatif bir kaynak tedavi olarak gözükmektedir.

Anahtar Kelimeler

• Kurkumin
• sinir hasarı
• mitokondriyal oksidatif stres
• morfin
• TRPV4 kanalı

Curcumin Reduces High-dose Morphine-Induced Apoptosis and Oxidative Neurotoxicity via TRPV4 Cation Channel Suppression

Abstract

Objective: Long-term and high-dose morphine (H-MRP) treatments for neuropathic pain cause the body to become extremely susceptible to morphine tolerance, which increases the amount of toxic reactive oxygen species (ROS), apoptosis, and calcium (Ca2+) entering the neuron. It has been known that curcumin (CRC) decreased these increases in ROS-damaged SH-SY5Y cells by blocking the TRPV4 cation channel. It has not been studied whether CRC can also suppress the high levels of ROS and apoptosis caused by H-MRP in SH-SY5Y cells by affecting TRPV4. So, the study was carried out to investigate whether CRC can suppress the high level of mitochondrial ROS and apoptosis. Materials and Methods: In the SH-SY5Y, four primary groups were induced as control, normal morphine (N-MRP) (50 µM for 24h), H-MRP (500 µM for 24h), H-MRP + CRC (5 µM for 24h). Results: While the incubations of TRPV4 antagonist (ruthenium red) and CRC decreased the H-MRP-induced increases of apoptosis, caspase-3, caspase-8, caspase-9, ROS, mitochondrial dysfunction, debris number, and lipid peroxidation levels, the TRPV4 agonist (GSK1016790A) stimulation further increased these levels. The CRC increased glutathione, glutathione peroxidase, live cell number, and cell viability percentage, all of which were decreased by H-MRP. Conclusions: The levels of H-MRP-induced neuronal death and mitochondrial oxidative stress were reduced by CRC treatment through TRPV4 inhibition. For H-MRP-induced mitochondrial oxidative neuronal injury, CRC is a potential treatment option.

Keywords

• Curcumin
• neuronal injury
• mitochondrial oxidative stress
• morphine
• TRPV4 channel

Kaynakça

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