Ahmet ALTUN

Kapsaisin apoptozu düzenleyerek SH-SY5Y hücrelerinde bupivakain anestezisinin neden olduğu nörotoksisiteyi hafifletmektedir

Amaç: Lokal anestezi için uygulanan bupivakain, nöronlarda ciddi nörotoksisite ve nörolojik komplikasyonlara neden olabilmektedir. Bupivakain aracılı toksik etkileri azaltabilen olası bir maddenin, cerrahi işlemler sırasında ve ağrı yönetimi sürecinde büyük ilgi görecektir. Bu kapsamda, kardiyoprotektif, anti-litojenik etki, anti-inflamatuar, analjezik, termojenik gibi çeşitli biyolojik etkileri ve gastrointestinal sistem üzerinde faydaları nedeniyle yoğun olarak araştırılan kırmızı biberin (Capsicum annuum) bir alkaloidi olan kapsaisinin nöroprotektif etkisini değerlendirdik. Yöntem: Bu çalışmada, kapsaisinin SH-SY5Y hücrelerinde bupivakain kaynaklı nörotoksisite üzerindeki in vitro etkisini araştırdık. Hücre canlılığı, XTT testi ile ölçüldü ve apoptoz, akış sitometri analizi ile ölçüldü. Bulgular: 1 mM'de bupivakaine maruz kalan hücrelerin canlılığında önemli bir azalma ile apoptoz indüksiyonunda kayda değer bir artış gözlemledik. Bupivakain ile tedavi edilen hücrelere artan konsantrasyonlarda kapsaisin uygulandığında bupivakain aracılı sitotoksisitenin azaldığını bulduk. Aynı zamanda kapsaisin, bupivakaine maruz kalan SH-SY5Y hücrelerinde apoptozu da azaltmıştır. Sonuç: Elde ettiğimiz sonuçlara göre, bupivakain aracılı nörotoksisiteye karşı kapsaisin uygulanmasının, nöronlardaki apoptoz yanıtının baskılanması yoluyla, alternatif bir nöroprotektif ajan olabileceği düşünülmektedir.

Anahtar Kelimeler:

Apoptoz, kapsaisin, SH-SY5Y., nörotoksisite, SH-SY5Y

Capsaicin attenuates bupivacaine anesthesia-induced neurotoxicity in SH-SY5Y cells by regulating apoptosis

Objective: Bupivacaine administered for local anesthesia can cause critical neurotoxicity and neurological dysfunctions. Any substance that can reduce bupivacaine-mediated toxic effects will be of great interest during surgical procedures and in the pain management process. In this context, we evaluated capsaicin, an alkaloid of Capsicum annuum (cayenne pepper), which has been intensively researched for its neuroprotective effect due to its various biological effects such as cardioprotective, antiinflammatory, analgesic, thermogenic, and benefits on the gastrointestinal tract. Methods: In this study, we researched the in vitro effect of capsaicin in SH-SY5Y cells with a model of bupivacaine-mediated neurotoxicity. Cell proliferation assay was handled by XTT, and apoptosis was determined by flow cytometry analysis. Results: We observed a notable increase in apoptosis induction with a significant decrease in the viability of cells exposed to bupivacaine at 1 mM. We found that bupivacaine-mediated cytotoxicity was reduced when increasing concentrations of capsaicin were applied to bupivacaine-treated cells. At the same time, capsaicin also reduced apoptosis in SH-SY5Y cells exposed to bupivacaine. Conclusion: According to our results, it is thought that the administration of capsaicin against bupivacaine-mediated neurotoxicity may be an alternative neuroprotective agent by suppressing the apoptosis response in neurons.

Keywords:

Apoptosis, capsaicin, neurotoxicity, SH-SY5Y,

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Petrar S, Montemurro T. Total local anesthetic administered is integral to the syndrome of local anesthetic systemic toxicity. Anesthesiology. 2014;121(5):1130-1131.
Verlinde M, Hollmann MW, Stevens MF, Hermanns H, Werdehausen R, Lirk P. Local anesthetic-induced neurotoxicity. Int J Mol Sci. 2016;17(3):339.
Yu X-J, Zhao W, Li Y-J, et al. Neurotoxicity comparison of two types of local anaesthetics: amide-bupivacaine versus ester-procaine. Sci Rep. 2017;7:45316.
Chaudhary A, Gour JK, Rizvi SI. Capsaicin has potent anti-oxidative effects in vivo through a mechanism which is nonreceptor mediated. Arch Physiol Biochem. 2019;1-7.
Zhang S, Wang D, Huang J, Hu Y, Xu Y. Application of Capsaicin as a potential new therapeutic drug in human cancers. J Clin Pharm Ther. 2020;45(1):16-28.
Yang F, Zheng J. Understand spiciness: mechanism of TRPV1 channel activation by capsaicin. Protein Cell. 2017;8(3):169-177.
Marinelli S, Pascucci T, Bernardi G, Puglisi-Allegra S, Mercuri NB. Activation of TRPV1 in the VTA excites dopaminergic neurons and increases chemical- and noxious-induced dopamine release in the nucleus accumbens. Neuropsychopharmacology. 2005;30(5):864-70.
Molot J, Sears M, Marshall LM, Bray RI. Neurological susceptibility to environmental exposures: pathophysiological mechanisms in neurodegeneration and multiple chemical sensitivity. Rev Environ Health. 2021;16.
Kukula O, Çiçekli MN, Şafak S, Günaydın C. Role of TRPV1 channels on glycogen synthase kinase-3β and oxidative stress in ouabain-induced bipolar disease. J Recept Signal Transduct Res. 2021;26:1-11.
Zhao W, Liu Z, Luo J, Ma C, Lai L, Xia Z, Xu S. The roles of PARP-1 and XPD and their potential interplay in repairing bupivacaine-induced neuron oxidative DNA damage. Aging (Albany NY). 2021;13(3):4274-4290.
Liu ZJ, Zhao W, Lei HY, Xu HL, Lai LY, Xu R, Xu SY. High Glucose Enhances Bupivacaine-Induced Neurotoxicity via MCU-Mediated Oxidative Stress in SH-SY5Y Cells. Oxid Med Cell Longev. 2019;2019:7192798.
Yang Z, Hu S, He Y, Ji L. LINC00665 rescues bupivacaine induced neurotoxicity in human neural cell of SH-SY5Y through has-miR-34a-5p. Brain Res Bull. 2021;177:210-216.
Park CJ, Park SA, Yoon TG, Lee SJ, Yum KW, Kim HJ. Bupivacaine induces apoptosis via ROS in the Schwann cell line. J Dent Res. 2005;84(9):852-7.
Naoi M, Maruyama W, Shamoto-Nagai M, Yi H, Akao Y, Tanaka M. Oxidative stress in mitochondria: decision to survival and death of neurons in neurodegenerative disorders. Mol Neurobiol. 2005;31(1-3):81-93.
Friederich P, Schmitz TP. Lidocaine-induced cell death in a human model of neuronal apoptosis. Eur J Anaesthesiol. 2002;19(8):564-70.
Wang S, Xia B, Qiao Z, Duan L, Wang G, Meng W, Liu Z, Wang Y, Zhang M. Tetramethylpyrazine attenuated bupivacaine-induced neurotoxicity in SH-SY5Y cells through regulating apoptosis, autophagy and oxidative damage. Drug Des Devel Ther. 2019;13:1187-1196.
Pezzoli M, Elhamdani A, Camacho S, et al. Dampened neural activity and abolition of epileptic-like activity in cortical slices by active ingredients of spices. Sci Rep. 2014;4:6825.
Lee TH, Lee JG, Yon JM, Oh KW, Baek IJ, Nahm SS, Lee BJ, Yun YW, Nam SY. Capsaicin prevents kainic acid-induced epileptogenesis in mice. Neurochem Int. 2011;58(6):634-40.
Huang M, Cheng G, Tan H, et al. Capsaicin protects cortical neurons against ischemia/reperfusion injury via down-regulating NMDA receptors. Exp Neurol. 2017;295:66-76.