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Nar Kabuğu Ekstresinin Sıçanlarda Paklitakselle İndüklenen Primer Nöron Hasarına Karşı Koruyucu Etkisi

Yıl 2018, Cilt: 8 Sayı: 3, 149 - 157, 01.12.2018

Öz

terapötikler ile tedavisinin tedaviyi desteklediği ve daha güçlü anti
kanser etki oluştuğu gösterilmiştir. Ancak nar kabuğunun kanser kemoterapisine bağlı gelişebilecek nörotoksisiteye karşı nasıl bir etki
göstereceği konusunda bir bilgi bulunmamaktadır. Çalışmamızda
güçlü antioksidan olan nar kabuğunun sıçanlarda paklitaksel ile indüklenen primer nöron hasarındaki etkilerini biyokimyasal ve moleküler analizler ile ortaya koymayı amaçladık.

Materyal ve Metot: Yeni doğan sıçan yavrularından elde edilen primer nöron hücre kültüründe paklitaksel toksisitesi indüklendi. PPE
200, 300 ve 400 mg/ml dozlarında koruyucu etki için paklitakselden
2 saat önce uygulandı.
Bulgular: Hücre canlılığı için yapılan MTT analizinde paklitaksel 24
saat sonunda nöron hasarı oluşturarak hücre canlılığını azaltmıştır.
PPE ise tüm dozlarda anlamlı bir şekilde paklitaksel toksisitesini
önleyerek hücre canlılığını korumuştur. PPE bu etkilerini oksidatif
stresi azaltarak, antioksidan kapasiteyi artırarak ve aynı zamanda
pro-inflamatuar sitokin olan TNF-α eksresyonunu ve apoptotik
proteinler olan caspase 9 ve 3 ekspresyonunu baskılayarak ortaya
koymuştur.
Sonuç: PPE antioksidan, anti-inflamatuar ve anti-apoptotik etkisi
ile paklitaksele bağlı gelişen primer nöron hasarını önlemiştir.

Kaynakça

  • 1. Schwab CL, English DP, Roque DM, Santin AD. Taxanes: their impact on gynecologic malignancy. Anticancer Drugs 2014; 25: 522-5.
  • 2. Bachegowda LS, Makower DF, Sparano JA. Taxanes: impact on breast cancer therapy. Anticancer Drugs 2014; 25: 512-1.
  • 3. Joshi M, Liu X, Belani CP. Taxanes, past, present, and future impact on non-small cell lung cancer. Anticancer Drugs 2014; 25:571–3.
  • 4. Letourneau P, Ressler A. Inhibition of neurite initiation and growth by taxol. J. Cell Biol.1984; 98: 1355-2.
  • 5. Scuteri A, Nicolini G, Miloso M, Bossi M, Cavaletti G, Windebank A et al. Paclitaxel toxicity in post-mitotic dorsal root ganglion (DRG) cells. Anticancer Res 2006; 26: 1065-70.
  • 6. Yang I, Siddique R, Hosmane S, Thakor N, Höke A. Compartmentalized microfluidic culture platform to study mechanism of paclitaxel-induced axonal degeneration. Exp Neurol 2009; 218: 124-8.
  • 7. Cetin D, Hacımuftuoglu A, Tatar A, Turkez H, Togar B. The in vitro protective effect of salicylic acid against paclitaxel and cisplatin-induced neurotoxicity. Cytotechnology 2016; 68: 1361-7.
  • 8. Ramezani F, Samadi N, Mostafavi-Pour Z. Sequential therapy of breast cancer cell lines with vitamin C and quercetin improves the efficacy of chemotherapeutic drugs. Nutr Cancer 2017; 69: 881-91.
  • 9. Syed DN, Afaq F, Mukhtar H. Pomagranate derived products for cancer chemoprevention. Semi. Cancer Biol 2007; 17:377-85.
  • 10. Borochow NH, Judeınstein S, Trıpler E, Hararı M, Greenberg A, Shomer I et al. Seasonal and cultivar variations in antioxidant and sensory quality of pomagranate (Punica granatum L.) fruit. J Food Compos Anal 2009; 22:189-95.
  • 11. Chandra R, Jadhav VT, Shrama J. Global scenario of pomagranate (Punica granatum L.) culture with special reference to India. Fruit Veg Cereal Sci 2010; 4:17-8.
  • 12. Gil MI, Tomas-Barberan FA, Hess-Pierce B, Holcroft DM, Kader AA. Antioxidant activity of pomegranate juice and its relationship with phenolic composition and processing. J Agric Food Chem 2000; 48:4581-9.
  • 13. Xu J, Guo CJ, Yang JJ, Wei JY, Li YF, Pang W et al. Intervention of antioxidant system function of aged rats by giving fruit juices with different antioxidant capacities. Zhonghua Yu Fang Yi Xue Za Zhi 2005; 39: 80-3.
  • 14. Singh B, Singh JP, Kaur A, Singh N. Phenolic compounds as beneficial phytochemicals in pomegranate (Punica granatum L.) peel: A review. Food Chem 2018;261:75-6.
  • 15. Bagheri M, Fazli M, Saeednia S, Kor A, Ahmadiankia N. Pomegranate peel extract inhibits expression of β-catenin, epithelial mesenchymal transition, and metastasis in triple negative breast cancer cells. Cell Mol Biol (Noisy-le-grand) 2018; 64:86-91.
  • 16. Chen XX, Lam KK, Feng YB, Xu K, Sze SC, Tang SC et al. Ellagitannins from Pomegranate Ameliorates 5-Fluorouracil-Induced Intestinal Mucositis in Rats while Enhancing Its Chemotoxicity against HT-29 Colorectal Cancer Cells through Intrinsic Apoptosis Induction. J Agric Food Chem 2018; 66:7054-64.
  • 17. Cadirci E, Halici Z, Yayla M, Toktay E, Bayir Y, Karakus E et al. Blocking of urotensin receptors as new target for treatment of carrageenan induced inflammation in rats. Peptides 2016; 82:35-43.
  • 18. Shemesh O, Spira M. Paclitaxel induces axonal microtubules polar reconfiguration and impaired organelle transport: implications for the pathogenesis of paclitaxel-induced polyneuropathy. Acta. Neuropathol 2010; 119: 235-48.
  • 19. Malgrange B, Delree P, Rigo JM, Baron H, Moonen G. Image analysis of neuritic regeneration by adult rat dorsal root ganglion neurons in culture: quantification of the neurotoxicity of anticancer agents and of its prevention by nerve growth factor or basic fibroblast growth factor but not brain-derived neurotrophic factor or neurotrophin-3. J Neurosci Methods 1994; 53: 111-22.
  • 20. Wang M, Davis A, Culver D, Glass J. WldS mice are resistant to paclitaxel (taxol) neuropathy. Ann Neurol 2002; 52: 442-7.
  • 21. Fotakis G, Timbrell JA. In vitro cytotoxicity assays: Comparison of LDH, neutral red, MTT and protein assay in hepatoma cell lines following exposure to cadmium chloride. Toxicol Lett 2006 ;160:171-7.
  • 22. Van de Loosdrecht AA, Beelen RH, Ossenkoppele GJ, Broekhoven MG, Langenhuijsen MM. A tetrazolium-based colorimetric MTT assay to quantitate human monocyte mediated cytotoxicity against leukemic cells from cell lines and patients with acute myeloid leukemia. J Immunol Methods 1994; 174: 31-20.
  • 23. Duggett NA, Griffiths LA, McKenna OE, de Santis V, Yongsanguanchai N, Mokori EB, Flatters SJ. Oxidative stress in the development, maintenance and resolution of paclitaxel-induced painful neuropathy. Neuroscience 2016; 333:13-26
  • 24. Liu S, Zhang X, Sun M, Xu T, Wang A. FoxO3a plays a key role in the protective effects of pomegranate peel extract against amikacin-induced ototoxicity. Int J Mol Med 2017; 40:175-81.
  • 25. Wang T, Men R, Hu M, Fan X, Yang X, Huang X et al. Protective effects of Punica granatum (pomegranate) peel extract on concanavalin A-induced autoimmune hepatitis in mice. Biomed Pharmacother 2018; 100:213-20.
  • 26. Hara Y, Sakagami H, Shi H, Abe T, Tamura N, Takeshima H et al. Partial Protection of Paclitaxel-induced Neurotoxicity by Antioxidants. In Vivo. 2018; 32:745-52.
  • 27. Kim HK, Zhang YP, Gwak YS, Abdi S. Phenyl N-tert-butylnitrone, a free radical scavenger, reduces mechanical allodynia in chemotherapy-induced neuropathic pain in rats. Anesthesiology 2010; 112:432–9.
  • 28. Doyle T, Chen Z, Muscoli C, Bryant L, Esposito E, Cuzzocrea S et al. Targeting the overproduction of peroxynitrite for the prevention and reversal of paclitaxel-induced neuropathic pain. J Neurosci 2012; 32:6149–60.
  • 29. Motor S, Ozturk S, Ozcan O, Gurpinar AB, Can Y, Yüksel R et al. Evaluation of total antioxidant status, total oxidant status and oxidative stress index in patients with alopecia areata. Int J Clin Exp Med 2014; 7:1089–93.
  • 30. Aslan R, Kutlu R, Civi S, Tasyurek E. The correlation of the total antioxidant status (TAS), total oxidant status (TOS) and paraoxonase activity (PON1) with smoking Author links open overlay panel. Clin Biochem 2014; 47:393-7.
  • 31. Abundan M, Çelik M, Almaz V, Geter S, Selek S, Koca B et al. Evaluation of S-100B and Oxidative Status before and after Treatment in Children with Bacterial Meningitis. Klin Derg 2012; 25: 67-70
  • 32. Meloni F. Tumor necrosis factor α. Biological aspects. Gior Itali di Chemi 1989; 36:29–37.40.
  • 33. MacEwan D J. TNF ligands and receptors – a matter of life and death. Brit J Pharm 2002;135 855-5.
  • 34. MacEwan D J. TNF receptor subtype signalling: differences and cellular consequences. Cell Sig 2002;14:477–92.
  • 35. Bogdan C, Ding A. Taxol, a microtubule-stabilizing antineoplastic agent, induces expression of tumor necrosis factor alpha and interleukin-1 in macrophages. J Leuk Biol 1992; 52:119–21.
  • 36. Wood SC, Tang X, Tesfamariam B. Paclitaxel potentiates inflammatory cytokine-induced prothrombotic molecules in endothelial cells. J Card Pharma 2010; 55:276–85.
  • 37. Wu Z, Wang S, Wu I, Mata M, Fink DJ. Activation of TLR-4 to produce tumour necrosis factor-α in neuropathic pain caused by paclitaxel. Eur J Pain 2015;19:889–98.
  • 38. Zhu Y, Yao Z, Wu Z, Mei Y, Wu M. Role of tumor necrosis factor alpha-induced protein 1 in paclitaxel resistance. Oncogene 2014;33:3246–55.
  • 39. Soojin P, Jin KS, Jun Yup K, Hwa-Jin S, YoungMi K, Yong CB. Anti-Inflammatory Effects of Pomegranate Peel Extract in THP-1 Cells Exposed to Particulate Matter PM10. Evid Based Complement Alternat Med 2016; 16:683-0.
  • 40. Maressa CM, Jocelem MS, Milena T, Danilo M, Patricia B, Hudson SB et al. Neuroprotective Effects of Pomegranate Peel Extract after Chronic Infusion with Amyloid-β Peptide in Mice. PLoS One 2016;9:11
  • 41. Jordan M, Wilson L. Microtubules as a target for anticancer drugs. Nat Rev Cancer 2004; 4:53-65.
  • 42. Christian W, Spencer G, Gary LJ. A turn-off mechanısm for antı-apoptotıc sıgnals. J Biol Chem 1998; 273:7141-7.
  • 43. Hitoshi T, Daisuke K, Tsubasa O, Masatoshi T, Takashi K. Paclitaxel induces neurotoxicity through endoplasmic reticulum stress. Biochem Biophys Res Commun 2013;437:151-5.
  • 44. Giorgia M, Michela T, Francesca C, Angelo Q, Franco T, Giuseppe L. Alpha-lipoic acid prevents mitochondrial damage and neurotoxicity in experimental chemotherapy neuropathy. Exp Neurol 2008; 214:276-84.
  • 45. Shuangyue L, Xiao Z, Meiling S, Tao X, Aimei W. FoxO3a plays a key role in the protective effects of pomegranate peel extract against amikacin-induced ototoxicity. Int J Mol Med 2017; 40:175-81.

Protective Effects of Pomegranate Peel Extract on Paclitaxel Induced Primary Neuron Damage in Rats

Yıl 2018, Cilt: 8 Sayı: 3, 149 - 157, 01.12.2018

Öz

Aim: The combination of chemotherapeutics and pomegranate
peel extract has been shown to have a stronger anti-cancer effect. However, there is no information about how pomegranate
peel extract will affect the neurotoxicity that may develop due to
cancer chemotherapy. In this study, we aimed to the effects of
strong antioxidant pomegranate peel extract on paclitaxel induced
primary neuron damage in newborn rats by biochemical and molecular analysis.
Material and Method: Paclitaxel toxicity was induced in the primary neuron cell culture derived from newborn rats. PPE 200, 300
and 400 mg/ml doses were applied 2 hours before the paclitaxel
for protective effect.
Results: In the MTT analysis, paclitaxel reduced cell viability by
caused neuronal damage at the end of 24 hours. PPE has demonstrated significant protective effect on cell viability by preventing paclitaxel toxicity at all doses. PPE was demonstrated its effects by reducing oxidative stress, increasing antioxidant capacity, and also by
suppressing the TNF-α expression which is pro-inflammatory cytokine, and caspase 9 and 3 expression which are apoptotic proteins.
Conclusion: PPE prevents primary neuron damage caused
paclitaxel by its antioxidant, anti-inflammatory and anti-apoptotic
effect

Kaynakça

  • 1. Schwab CL, English DP, Roque DM, Santin AD. Taxanes: their impact on gynecologic malignancy. Anticancer Drugs 2014; 25: 522-5.
  • 2. Bachegowda LS, Makower DF, Sparano JA. Taxanes: impact on breast cancer therapy. Anticancer Drugs 2014; 25: 512-1.
  • 3. Joshi M, Liu X, Belani CP. Taxanes, past, present, and future impact on non-small cell lung cancer. Anticancer Drugs 2014; 25:571–3.
  • 4. Letourneau P, Ressler A. Inhibition of neurite initiation and growth by taxol. J. Cell Biol.1984; 98: 1355-2.
  • 5. Scuteri A, Nicolini G, Miloso M, Bossi M, Cavaletti G, Windebank A et al. Paclitaxel toxicity in post-mitotic dorsal root ganglion (DRG) cells. Anticancer Res 2006; 26: 1065-70.
  • 6. Yang I, Siddique R, Hosmane S, Thakor N, Höke A. Compartmentalized microfluidic culture platform to study mechanism of paclitaxel-induced axonal degeneration. Exp Neurol 2009; 218: 124-8.
  • 7. Cetin D, Hacımuftuoglu A, Tatar A, Turkez H, Togar B. The in vitro protective effect of salicylic acid against paclitaxel and cisplatin-induced neurotoxicity. Cytotechnology 2016; 68: 1361-7.
  • 8. Ramezani F, Samadi N, Mostafavi-Pour Z. Sequential therapy of breast cancer cell lines with vitamin C and quercetin improves the efficacy of chemotherapeutic drugs. Nutr Cancer 2017; 69: 881-91.
  • 9. Syed DN, Afaq F, Mukhtar H. Pomagranate derived products for cancer chemoprevention. Semi. Cancer Biol 2007; 17:377-85.
  • 10. Borochow NH, Judeınstein S, Trıpler E, Hararı M, Greenberg A, Shomer I et al. Seasonal and cultivar variations in antioxidant and sensory quality of pomagranate (Punica granatum L.) fruit. J Food Compos Anal 2009; 22:189-95.
  • 11. Chandra R, Jadhav VT, Shrama J. Global scenario of pomagranate (Punica granatum L.) culture with special reference to India. Fruit Veg Cereal Sci 2010; 4:17-8.
  • 12. Gil MI, Tomas-Barberan FA, Hess-Pierce B, Holcroft DM, Kader AA. Antioxidant activity of pomegranate juice and its relationship with phenolic composition and processing. J Agric Food Chem 2000; 48:4581-9.
  • 13. Xu J, Guo CJ, Yang JJ, Wei JY, Li YF, Pang W et al. Intervention of antioxidant system function of aged rats by giving fruit juices with different antioxidant capacities. Zhonghua Yu Fang Yi Xue Za Zhi 2005; 39: 80-3.
  • 14. Singh B, Singh JP, Kaur A, Singh N. Phenolic compounds as beneficial phytochemicals in pomegranate (Punica granatum L.) peel: A review. Food Chem 2018;261:75-6.
  • 15. Bagheri M, Fazli M, Saeednia S, Kor A, Ahmadiankia N. Pomegranate peel extract inhibits expression of β-catenin, epithelial mesenchymal transition, and metastasis in triple negative breast cancer cells. Cell Mol Biol (Noisy-le-grand) 2018; 64:86-91.
  • 16. Chen XX, Lam KK, Feng YB, Xu K, Sze SC, Tang SC et al. Ellagitannins from Pomegranate Ameliorates 5-Fluorouracil-Induced Intestinal Mucositis in Rats while Enhancing Its Chemotoxicity against HT-29 Colorectal Cancer Cells through Intrinsic Apoptosis Induction. J Agric Food Chem 2018; 66:7054-64.
  • 17. Cadirci E, Halici Z, Yayla M, Toktay E, Bayir Y, Karakus E et al. Blocking of urotensin receptors as new target for treatment of carrageenan induced inflammation in rats. Peptides 2016; 82:35-43.
  • 18. Shemesh O, Spira M. Paclitaxel induces axonal microtubules polar reconfiguration and impaired organelle transport: implications for the pathogenesis of paclitaxel-induced polyneuropathy. Acta. Neuropathol 2010; 119: 235-48.
  • 19. Malgrange B, Delree P, Rigo JM, Baron H, Moonen G. Image analysis of neuritic regeneration by adult rat dorsal root ganglion neurons in culture: quantification of the neurotoxicity of anticancer agents and of its prevention by nerve growth factor or basic fibroblast growth factor but not brain-derived neurotrophic factor or neurotrophin-3. J Neurosci Methods 1994; 53: 111-22.
  • 20. Wang M, Davis A, Culver D, Glass J. WldS mice are resistant to paclitaxel (taxol) neuropathy. Ann Neurol 2002; 52: 442-7.
  • 21. Fotakis G, Timbrell JA. In vitro cytotoxicity assays: Comparison of LDH, neutral red, MTT and protein assay in hepatoma cell lines following exposure to cadmium chloride. Toxicol Lett 2006 ;160:171-7.
  • 22. Van de Loosdrecht AA, Beelen RH, Ossenkoppele GJ, Broekhoven MG, Langenhuijsen MM. A tetrazolium-based colorimetric MTT assay to quantitate human monocyte mediated cytotoxicity against leukemic cells from cell lines and patients with acute myeloid leukemia. J Immunol Methods 1994; 174: 31-20.
  • 23. Duggett NA, Griffiths LA, McKenna OE, de Santis V, Yongsanguanchai N, Mokori EB, Flatters SJ. Oxidative stress in the development, maintenance and resolution of paclitaxel-induced painful neuropathy. Neuroscience 2016; 333:13-26
  • 24. Liu S, Zhang X, Sun M, Xu T, Wang A. FoxO3a plays a key role in the protective effects of pomegranate peel extract against amikacin-induced ototoxicity. Int J Mol Med 2017; 40:175-81.
  • 25. Wang T, Men R, Hu M, Fan X, Yang X, Huang X et al. Protective effects of Punica granatum (pomegranate) peel extract on concanavalin A-induced autoimmune hepatitis in mice. Biomed Pharmacother 2018; 100:213-20.
  • 26. Hara Y, Sakagami H, Shi H, Abe T, Tamura N, Takeshima H et al. Partial Protection of Paclitaxel-induced Neurotoxicity by Antioxidants. In Vivo. 2018; 32:745-52.
  • 27. Kim HK, Zhang YP, Gwak YS, Abdi S. Phenyl N-tert-butylnitrone, a free radical scavenger, reduces mechanical allodynia in chemotherapy-induced neuropathic pain in rats. Anesthesiology 2010; 112:432–9.
  • 28. Doyle T, Chen Z, Muscoli C, Bryant L, Esposito E, Cuzzocrea S et al. Targeting the overproduction of peroxynitrite for the prevention and reversal of paclitaxel-induced neuropathic pain. J Neurosci 2012; 32:6149–60.
  • 29. Motor S, Ozturk S, Ozcan O, Gurpinar AB, Can Y, Yüksel R et al. Evaluation of total antioxidant status, total oxidant status and oxidative stress index in patients with alopecia areata. Int J Clin Exp Med 2014; 7:1089–93.
  • 30. Aslan R, Kutlu R, Civi S, Tasyurek E. The correlation of the total antioxidant status (TAS), total oxidant status (TOS) and paraoxonase activity (PON1) with smoking Author links open overlay panel. Clin Biochem 2014; 47:393-7.
  • 31. Abundan M, Çelik M, Almaz V, Geter S, Selek S, Koca B et al. Evaluation of S-100B and Oxidative Status before and after Treatment in Children with Bacterial Meningitis. Klin Derg 2012; 25: 67-70
  • 32. Meloni F. Tumor necrosis factor α. Biological aspects. Gior Itali di Chemi 1989; 36:29–37.40.
  • 33. MacEwan D J. TNF ligands and receptors – a matter of life and death. Brit J Pharm 2002;135 855-5.
  • 34. MacEwan D J. TNF receptor subtype signalling: differences and cellular consequences. Cell Sig 2002;14:477–92.
  • 35. Bogdan C, Ding A. Taxol, a microtubule-stabilizing antineoplastic agent, induces expression of tumor necrosis factor alpha and interleukin-1 in macrophages. J Leuk Biol 1992; 52:119–21.
  • 36. Wood SC, Tang X, Tesfamariam B. Paclitaxel potentiates inflammatory cytokine-induced prothrombotic molecules in endothelial cells. J Card Pharma 2010; 55:276–85.
  • 37. Wu Z, Wang S, Wu I, Mata M, Fink DJ. Activation of TLR-4 to produce tumour necrosis factor-α in neuropathic pain caused by paclitaxel. Eur J Pain 2015;19:889–98.
  • 38. Zhu Y, Yao Z, Wu Z, Mei Y, Wu M. Role of tumor necrosis factor alpha-induced protein 1 in paclitaxel resistance. Oncogene 2014;33:3246–55.
  • 39. Soojin P, Jin KS, Jun Yup K, Hwa-Jin S, YoungMi K, Yong CB. Anti-Inflammatory Effects of Pomegranate Peel Extract in THP-1 Cells Exposed to Particulate Matter PM10. Evid Based Complement Alternat Med 2016; 16:683-0.
  • 40. Maressa CM, Jocelem MS, Milena T, Danilo M, Patricia B, Hudson SB et al. Neuroprotective Effects of Pomegranate Peel Extract after Chronic Infusion with Amyloid-β Peptide in Mice. PLoS One 2016;9:11
  • 41. Jordan M, Wilson L. Microtubules as a target for anticancer drugs. Nat Rev Cancer 2004; 4:53-65.
  • 42. Christian W, Spencer G, Gary LJ. A turn-off mechanısm for antı-apoptotıc sıgnals. J Biol Chem 1998; 273:7141-7.
  • 43. Hitoshi T, Daisuke K, Tsubasa O, Masatoshi T, Takashi K. Paclitaxel induces neurotoxicity through endoplasmic reticulum stress. Biochem Biophys Res Commun 2013;437:151-5.
  • 44. Giorgia M, Michela T, Francesca C, Angelo Q, Franco T, Giuseppe L. Alpha-lipoic acid prevents mitochondrial damage and neurotoxicity in experimental chemotherapy neuropathy. Exp Neurol 2008; 214:276-84.
  • 45. Shuangyue L, Xiao Z, Meiling S, Tao X, Aimei W. FoxO3a plays a key role in the protective effects of pomegranate peel extract against amikacin-induced ototoxicity. Int J Mol Med 2017; 40:175-81.
Toplam 45 adet kaynakça vardır.

Ayrıntılar

Birincil Dil Türkçe
Bölüm Araştırma Makalesi
Yazarlar

Muhammed Yayla Bu kişi benim

Damla Çetin Bu kişi benim

Çağlar Demirbağ Bu kişi benim

Pınar Aksu Kılıçle Bu kişi benim

Yayımlanma Tarihi 1 Aralık 2018
Yayımlandığı Sayı Yıl 2018 Cilt: 8 Sayı: 3

Kaynak Göster

APA Yayla, M., Çetin, D., Demirbağ, Ç., Aksu Kılıçle, P. (2018). Nar Kabuğu Ekstresinin Sıçanlarda Paklitakselle İndüklenen Primer Nöron Hasarına Karşı Koruyucu Etkisi. Kafkas Journal of Medical Sciences, 8(3), 149-157.
AMA Yayla M, Çetin D, Demirbağ Ç, Aksu Kılıçle P. Nar Kabuğu Ekstresinin Sıçanlarda Paklitakselle İndüklenen Primer Nöron Hasarına Karşı Koruyucu Etkisi. Kafkas Journal of Medical Sciences. Aralık 2018;8(3):149-157.
Chicago Yayla, Muhammed, Damla Çetin, Çağlar Demirbağ, ve Pınar Aksu Kılıçle. “Nar Kabuğu Ekstresinin Sıçanlarda Paklitakselle İndüklenen Primer Nöron Hasarına Karşı Koruyucu Etkisi”. Kafkas Journal of Medical Sciences 8, sy. 3 (Aralık 2018): 149-57.
EndNote Yayla M, Çetin D, Demirbağ Ç, Aksu Kılıçle P (01 Aralık 2018) Nar Kabuğu Ekstresinin Sıçanlarda Paklitakselle İndüklenen Primer Nöron Hasarına Karşı Koruyucu Etkisi. Kafkas Journal of Medical Sciences 8 3 149–157.
IEEE M. Yayla, D. Çetin, Ç. Demirbağ, ve P. Aksu Kılıçle, “Nar Kabuğu Ekstresinin Sıçanlarda Paklitakselle İndüklenen Primer Nöron Hasarına Karşı Koruyucu Etkisi”, Kafkas Journal of Medical Sciences, c. 8, sy. 3, ss. 149–157, 2018.
ISNAD Yayla, Muhammed vd. “Nar Kabuğu Ekstresinin Sıçanlarda Paklitakselle İndüklenen Primer Nöron Hasarına Karşı Koruyucu Etkisi”. Kafkas Journal of Medical Sciences 8/3 (Aralık 2018), 149-157.
JAMA Yayla M, Çetin D, Demirbağ Ç, Aksu Kılıçle P. Nar Kabuğu Ekstresinin Sıçanlarda Paklitakselle İndüklenen Primer Nöron Hasarına Karşı Koruyucu Etkisi. Kafkas Journal of Medical Sciences. 2018;8:149–157.
MLA Yayla, Muhammed vd. “Nar Kabuğu Ekstresinin Sıçanlarda Paklitakselle İndüklenen Primer Nöron Hasarına Karşı Koruyucu Etkisi”. Kafkas Journal of Medical Sciences, c. 8, sy. 3, 2018, ss. 149-57.
Vancouver Yayla M, Çetin D, Demirbağ Ç, Aksu Kılıçle P. Nar Kabuğu Ekstresinin Sıçanlarda Paklitakselle İndüklenen Primer Nöron Hasarına Karşı Koruyucu Etkisi. Kafkas Journal of Medical Sciences. 2018;8(3):149-57.