Chemotherapy-induced peripheral neuropathy in the neuronal cells model

Year 2024, Volume: 49 Issue: 3, 858 - 859, 30.09.2024

Simge Ünay

https://doi.org/10.17826/cumj.1439488

Abstract

This research aims to investigate the impacts of quercetin and low-level laser therapy (LLLT) on undifferentiated and nerve growth factor-differentiated PC12 cells experiencing cisplatin-induced peripheral neuropathy. PC12 cells treated with cisplatin were simultaneously exposed to quercetin and LLLT. We evaluated the effects of quercetin and LLLT on the expression of GAP-43 and Synapsin I genes through real-time PCR, cell viability using MTT assay, apoptosis induction via Annexin and dead assay, mitochondrial potential alterations using a mitopotential assay, and lactate dehydrogenase activity analysis in cells. Our findings revealed that cisplatin led to increased apoptosis, mitochondrial dysfunction, and LDH activity, while reducing cell viability and inhibiting the expression of GAP-43 and Synapsin I genes in both undifferentiated and differentiated PC12 cells. However, the application of quercetin and LLLT resulted in decreased apoptosis, mitochondrial potential alterations, and lactate dehydrogenase activity. We propose further investigation into the in vivo effects of quercetin and low-level laser therapy on cisplatin-induced peripheral neuropathy, as well as exploring the molecular relationship between quercetin and low-level laser therapy.

Keywords

Neuronal Cells, Cisplatin, Chemotherapy-induced peripheral neuropathy

Nöronal hücre modelinde kemoterapiye bağlı periferik nöropati

Abstract

Bu araştırma, quercetin ve düşük seviyeli lazer tedavisinin (LLLT) sisplatin kaynaklı periferik nöropati yaşayan farklılaşmamış ve sinir büyüme faktörü ile farklılaşmış PC12 hücreleri üzerindeki etkilerini araştırmayı amaçlamaktadır. Sisplatin ile muamele edilen PC12 hücreleri eş zamanlı olarak kuersetin ve LLLT'ye maruz bırakıldı. Kuersetin ve LLLT'nin GAP-43 ve Sinapsin I genlerinin ekspresyonu üzerindeki etkilerini gerçek zamanlı PCR, MTT testi ile hücre canlılığı, Annexin ve ölü testi ile apoptoz indüksiyonu, mitopotansiyel testi ile mitokondriyal potansiyel değişiklikleri ve hücrelerde laktat dehidrojenaz aktivite analizi ile değerlendirdik. Bulgularımız sisplatinin hem farklılaşmamış hem de farklılaşmış PC12 hücrelerinde apoptoz, mitokondriyal disfonksiyon ve LDH aktivitesinde artışa yol açarken hücre canlılığını azalttığını ve GAP-43 ve Sinapsin I genlerinin ekspresyonunu inhibe ettiğini ortaya koymuştur. Bununla birlikte, kuersetin ve LLLT uygulaması apoptoz, mitokondriyal potansiyel değişiklikleri ve laktat dehidrojenaz aktivitesinde azalma ile sonuçlanmıştır. Quercetin ve düşük seviyeli lazer tedavisinin sisplatin kaynaklı periferik nöropati üzerindeki in vivo etkilerinin yanı sıra quercetin ve düşük seviyeli lazer tedavisi arasındaki moleküler ilişkinin araştırılmasını öneriyoruz.

Keywords

Nöronal Hücreler, Sisplatin, Kemoterapiye bağlı periferik nöropati

References

• Bernhardson BM, Tishelman C, Rutqvist LE. Chemosensory changes experienced by patients undergoing cancer chemotherapy: a qualitative interview study. J Pain Symptom Manage. 2007;34:403–12.
• Zajaczkowską R, Kocot-Kępska M, Leppert W, Wrzosek A, Mika J, Wordliczek J. Mechanisms of chemotherapy-induced peripheral neuropathy. Int J Mol Sci. 2019;20:1451.
• Dhawan S, Andrews R, Kumar L, Wadhwa S, Shukla G. A randomized controlled trial to assess the effectiveness of muscle strengthening and balancing exercises on chemotherapy-induced peripheral neuropathic pain and quality of life among cancer patients. Cancer Nurs. 2020;43:269–80.
• Staff NP, Grisold A, Grisold W, Windebank AJ. Chemotherapy-induced peripheral neuropathy: A current review. Ann Neurol. 2017;81:772–81.
• Shipley MM, Mangold CA, Szpara ML. Differentiation of the SH-SY5Y human neuroblastoma cell line. J Vis Exp. 2016; 2016:53193.
• Wang XM, Lehky TJ, Brell JM, Dorsey SG. Discovering cytokines as targets for chemotherapy-induced painful peripheral neuropathy. Cytokine. 2012;59:3–9.
• Hausheer FH, Schilsky RL, Bain S, Berghorn EJ, Lieberman F. Diagnosis, management, and evaluation of chemotherapy-induced peripheral neuropathy. Semin Oncol. 2006;33:15–49.
• Kovalevich J, Langford D. Considerations for the use of SH-SY5Y neuroblastoma cells in neurobiology. Methods Mol Biol. 2013;1078:9–21.
• Wiatrak B, Kubis-Kubiak A, Piwowar A, Barg E. PC12 cell line: cell types, coating of culture vessels, differentiation and other culture conditions. Cells. 2020;9:958.
• Unay S, Bilgin MD. Investigation of effects of quercetin and low-level laser therapy in cisplatin-induced in vitro peripheral neuropathy model. Lasers Med Sci. 2023;38:49.