Araştırma Makalesi
Reno-Protective Effects of 6-Shogaol on Kidney Tissue in Cecal Ligation and Puncture-Induced Polymicrobial Sepsis Rat Model
Öz
Sepsis is a life-threatening syndrome that may lead to multiple organ dysfunction with high mortality. A deformation or puncture in the intestinal barrier plays an important role in sepsis-induced multiple organ failure. The protective effects of 6-Shogaol (6-SHO) on renal injury caused by cecal ligation and puncture (CLP) was investigated. Experimental animals were divided into 4 groups and planned as follows; sham, CLP, CLP+DMSO, and CLP+6-SHO. In CLP + 6-SHO group, 20 mg/kg 6-SHO was administered intraperitoneally before the CLP model. The levels of antioxidant molecules (total antioxidant status (TAS) and superoxide dismutase (SOD)), oxidant molecules (total oxidant status (TOS), malondialdehyde (MDA) and myeloperoxidase (MPO)) and proinflammatory cytokines (tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β)) were measured by homogenizing in collected kidney tissues. Statistical analyzes were performed via ANOVA. In CLP groups, antioxidant molecule levels decreased while oxidant molecule values elevated. Similarly, proinflammatory cytokine levels were found high in CLP groups. In CLP+6-SHO group, oxidant molecules, MPO, and proinflammatory cytokine levels diminished, and antioxidant molecules increased. 6-SHO application has been shown to be effective against oxidative renal injury caused by the CLP-induced polymicrobial sepsis model.
Anahtar Kelimeler
6-Shogaol Cecal ligation and puncture Kidney Inflammation Oxidative stress
Destekleyen Kurum
Yok
Proje Numarası
Yok
Teşekkür
We would like to thanks all participants and also Kardelen Erdoğan and Yaylagülü Yaman, undergraduates of Atatürk University Nursing Faculty.
Kaynakça
- 1. Wang HF., Li Y., Wang YQ., Li HJ., Dou L., 2019. MicroRNA-494-3p alleviates inflammatory response in sepsis by targeting TLR6. Eur Rev Med Pharmacol Sci, 23, 2971-2977. 2. Sungkar Y., Considine J., Hutchinson A., 2018. Implementation of guidelines for sepsis management in emergency departments: A systematic review. Australas Emerg Care, 21, 111-120. 3. Schrier RW., Wang W., 2004. Acute renal failure and sepsis. N Engl J Med, 351, 159-169. 4. Tsiotou AG., Sakorafas GH., Anagnostopoulos G., Bramis J., 2005. Septic shock; current pathogenetic concepts from a clinical perspective. Med Sci Monit, 11, Ra76-85. 5. Lee DM., Hoffman WH., Carl GF., Khichi M., Cornwell PE., 2002. Lipid peroxidation and antioxidant vitamins prior to, during, and after correction of diabetic ketoacidosis. J Diabetes Complications, 16, 294-300. 6. Tok A., Sener E., Albayrak A., Cetin N., Polat B., Suleyman B., Akcay F., Suleyman H., 2012. Effect of mirtazapine on oxidative stress created in rat kidneys by ischemia-reperfusion. Ren Fail, 34, 103-110. 7. Ansari RA., Aswal BS., Chander R., Dhawan BN., Garg NK., Kapoor NK., Kulshreshtha DK., Mehdi H., Mehrotra BN., Patnaik GK., 1988. Hepatoprotective activity of kutkin-the iridoid glycoside mixture of Picrorhiza kurrooa. Indian J Med Res, 87, 401-404. 8. Erel O., 2005. A new automated colorimetric method for measuring total oxidant status. Clin Biochem, 38, 1103-1111. 9. Akdemir EFN., Tanyeli A., 2019. The Antioxidant Effect of Fraxin against Acute Organ Damage in Polymicrobial Sepsis Model induced by Cecal Ligation and Puncture. TJOS, 4, 22-29. 10. de Jong HK., van der Poll T., Wiersinga WJ., 2010. The systemic pro-inflammatory response in sepsis. J Innate Immun, 2, 422-430. 11. Gaut JP., Yeh GC., Tran HD., Byun J., Henderson JP., Richter GM., Brennan ML., Lusis AJ., Belaaouaj A., Hotchkiss RS., Heinecke JW., 2001. Neutrophils employ the myeloperoxidase system to generate antimicrobial brominating and chlorinating oxidants during sepsis. Proc Natl Acad Sci U S A, 98, 11961-11966. 12. Han Q., Yuan Q., Meng X., Huo J., Bao Y., Xie G. 2017. 6-Shogaol attenuates LPS-induced inflammation in BV2 microglia cells by activating PPAR-γ. Oncotarget, 8, 42001-42006. 13. Na JY., Song K., Lee JW., Kim S., Kwon J., 2016. Pretreatment of 6-shogaol attenuates oxidative stress and inflammation in middle cerebral artery occlusion-induced mice. Eur J Pharmacol, 788, 241-247. 14. Na JY., Song K., Lee JW., Kim S., Kwon J., 2016. 6-Shogaol has anti-amyloidogenic activity and ameliorates Alzheimer's disease via CysLT1R-mediated inhibition of cathepsin B. Biochem Biophys Res Commun, 477, 96-102. 15. Moon M., Kim HG., Choi JG., Oh H., Lee PK., Ha SK., Kim SY., Park Y., Huh Y., Oh MS., 2014. 6-Shogaol, an active constituent of ginger, attenuates neuroinflammation and cognitive deficits in animal models of dementia. Biochem Biophys Res Commun, 449, 8-13. 16. Akdemir EFN., Yildirim S., Kandemir FM., Tanyeli A., Küçükler S., Bahaeddin DM., 2019. Protective effects of gallic acid on doxorubicin-induced cardiotoxicity; an experimantal study. Arch Physiol Biochem, 26, 1-8. 17. Han SJ., Kim M., D'Agati VD., Lee HT., 2019. 6-Shogaol protects against ischemic acute kidney injury by modulating NF-κB and heme oxygenase-1 pathways. Am J Physiol Renal Physiol, 317, F743-F756. 18. Ohkawa H., Ohishi N., Yagi K., 1979. Assay for lipid peroxides in animal-tissues by thiobarbituric acid reaction. Anal Biochem, 95, 351-358. 19. Harma M., Harma M., Kocyigit A., Erel O., 2005. Increased DNA damage in patients with complete hydatidiform mole. Mutat Res, 583, 49-54. 20. Bradley PP., Priebat DA., Christensen RD., Rothstein G., 1982. Measurement of cutaneous inflammation: estimation of neutrophil content with an enzyme marker. J Invest Dermatol, 78, 206-209. 21. Sun Y., Oberley LW., Li Y., 1988. A simple method for clinical assay of superoxide-dismutase. Clin Chem, 34, 497-500. 22. Cecconi M., Evans L., Levy M., Rhodes A., 2018. Sepsis and septic shock. Lancet, 392, 75-87. 23. Xu G., Mo L., Wu C., Shen X., Dong H., Yu L., Pan P., Pan K., 2019. The miR-15a-5p-XIST-CUL3 regulatory axis is important for sepsis-induced acute kidney injury. Ren Fail, 41, 955-966. 24. Srisawat N., Lawsin L., Uchino S., Bellomo R., Kellum JA., 2010. Cost of acute renal replacement therapy in the intensive care unit: results from the beginning and ending supportive therapy for the kidney (BEST Kidney) study. Crit Care, 14, R46. 25. Rhodes A., Evans LE., Alhazzani W., Levy MM., Antonelli M., Ferrer R., Kumar A., Sevransky JE., Sprung CL., Nunnally ME., Rochwerg B., Rubenfeld GD., Angus DC., Annane D., Beale RJ., Bellinghan GJ., Bernard GR., Chiche JD., Coopersmith C., De Backer DP., French CJ., Fujishima S., Gerlach H., Hidalgo JL., Hollenberg SM., Jones AE., Karnad DR., Kleinpell RM., Koh Y., Lisboa TC., Machado FR., Marini JJ., Marshall JC., Mazuski JE., McIntyre LA., McLean AS., Mehta S., Moreno RP., Myburgh J., Navalesi P., Nishida O., Osborn TM., Perner A., Plunkett CM., Ranieri M., Schorr CA., Seckel MA., Seymour CW., Shieh L., Shukri KA., Simpson SQ., Singer M., Thompson BT., Townsend SR., Van der Poll T., Vincent JL., Wiersinga WJ., Zimmerman JL., Dellinger RP., 2017. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock. Intensive Care Med, 43, 304-377. 26. Zolali E., Hamishehkar H., Maleki-Dizaji N., Majidi Zolbanin N., Ghavimi H., Kouhsoltani M., Asgharian P., 2014. Selenium effect on oxidative stress factors in septic rats. Adv Pharm Bull, 4, 289-293. 27. Buras JA., Holzmann B., Sitkovsky M., 2005. Animal models of sepsis: setting the stage. Nat Rev Drug Discov, 4, 854-865. 28. Damas P., Ledoux D., Nys M., Vrindts Y., De Groote D., Franchimont P., Lamy M., 1992. Cytokine serum level during severe sepsis in human IL-6 as a marker of severity. Ann Surg, 215, 356-362. 29. De Jong HK., Van Der Poll T., Wiersinga WJ., 2010. The systemic pro-inflammatory response in sepsis. J Innate Immun, 2, 422-430. 30. Cakir M., Polat A., Tekin S., Vardi N., Taslidere E., Rumeysa DZ., Tanbek K., 2015. The effect of dexmedetomidine against oxidative and tubular damage induced by renal ischemia reperfusion in rats. Ren Fail, 37, 704-708. 31. Nie H., Xue X., Liu G., Guan G., Liu H., Sun L., Zhao L., Wang X., Chen Z., 2016. Nitro-oleic acid ameliorates oxygen and glucose deprivation/re-oxygenation triggered oxidative stress in renal tubular cells via activation of Nrf2 and suppression of NADPH oxidase. Free Radic Res, 50, 1200-1213. 32. Han HS., Kim KB., Jung JH., An IS., Kim YJ., An S., 2018. Anti-apoptotic, antioxidant and anti-aging effects of 6-shogaol on human dermal fibroblasts. Biomedical Dermatology, 2, 1-8. 33. Ma Q. 2013. Role of nrf2 in oxidative stress and toxicity. Annu Rev Pharmacol Toxicol, 53, 401-426. 34. Kadioglu E., Teksen Y., Kocak C., Kocak FE., 2019. Beneficial effects of bardoxolone methyl, an Nrf2 activator, on crush-related acute kidney injury in rats. Eur J Trauma Emerg Surg, 1-10. 35. Perkins ND., 2000. The Rel/NF-kappa B family: friend and foe. Trends Biochem Sci, 25, 434-440. 36. Brown KA., Brain SD., Pearson JD., Edgeworth JD., Lewis SM., Treacher DF., 2006. Neutrophils in development of multiple organ failure in sepsis. Lancet, 368, 157-169. 37. Cassatella MA., 1999. Neutrophil-derived proteins: selling cytokines by the pound. Adv Immunol, 73, 369-509. 38. Mortaz E., Alipoor SD., Adcock IM., Mumby S., Koenderman L., 2018. Update on Neutrophil Function in Severe Inflammation. Front Immunol, 9, 2171. 39. Lu TF., Yang TH., Zhong CP., Shen C., Lin WW., Gu GX., Xia Q., Xu N., 2018. Dual Effect of Hepatic Macrophages on Liver Ischemia and Reperfusion Injury during Liver Transplantation. Immune Netw, 18, e24. 40. Ozkanlar FA., Halıcı Z., Uyanık MH., 2016. Comparison of the therapeutic effects of antibiotic, steroid, and vitamin K during early sepsis in laboratory animals. Atatürk Üniversitesi Vet. Bil. Derg, 11, 13-21. 41. Wang CY., Hsieh MJ., Hsieh IC., Shie SS., Ho MY., Yeh JK., Tsai ML., Yang CH., Hung KC., Wang CC., Wen MS., 2016. CLOCK modulates survival and acute lung injury in mice with polymicrobial sepsis. Biochem Biophys Res Commun, 478, 935-941
Çekal Ligasyon ve Delmeye Bağlı Polimikrobiyal Sepsis Sıçan Modelinde 6-Shogaol'ün Böbrek Dokusu Üzerine Renoprotektif Etkileri
Öz
Sepsis, yüksek mortalite ile çoklu organ disfonksiyonuna ilerleyebilen hayatı tehdit eden bir sendromdur. Bağırsak bariyerinde gerçekleşen bir deformasyon veya delinme sepsise bağlı çoklu organ yetmezliğinde önemli bir rol oynar. 6-Shogaol'ün (6-SHO) çekal ligasyon ve delmeye (CLD) bağlı böbrek hasarındaki koruyucu etkileri araştırıldı. Deney hayvanları 4 gruba ayrıldı ve şu şekilde planlandı; sham, CLD, CLD + DMSO ve CLD + 6-SHO. CLD + 6-SHO grubunda, CLD'den önce 6-SHO enjekte edildi (20 mg/kg, intraperitoneal). Toplanan böbrek dokuları homojenize edilerek antioksidan moleküller (total antioksidan kapasite (TAS) ve süperoksit dismütaz (SOD)), oksidan moleküller (total oksidan kapasite (TOS), malondialdehit (MDA) ve myeloperoksidaz (MPO)) ve pro-inflamatuar sitokinlerin (tümör nekroz faktör-α (TNF-α) ve interlökin-1β (IL-1β)) düzeyleri ölçüldü. İstatistiksel analizler ANOVA ile yapıldı. CLD gruplarında antioksidan moleküller; seviyeleri azalırken oksidan molekülerin seviyeleri yükseldi. Benzer şekilde pro-inflamatuar sitokin seviyeleri de CLD gruplarında yüksek bulundu. 6-SHO ile tedavi edilen grupta oksidan moleküllerin ve proinflamatuar sitokin seviyelerinin azaldığı ve antioksidan moleküllerin seviyeleri yüksek bulundu. 6-SHO uygulamasının CLD ile indüklenen polimikrobiyal sepsis modeli tarafından üretilen oksidatif böbrek hasarına karşı etkili olduğunu gösterilmiştir.
Anahtar Kelimeler
6-Shogaol Böbrek Çekal ligasyon ve delinme İnflamasyon Oksidatif stres
Proje Numarası
Yok
Kaynakça
- 1. Wang HF., Li Y., Wang YQ., Li HJ., Dou L., 2019. MicroRNA-494-3p alleviates inflammatory response in sepsis by targeting TLR6. Eur Rev Med Pharmacol Sci, 23, 2971-2977. 2. Sungkar Y., Considine J., Hutchinson A., 2018. Implementation of guidelines for sepsis management in emergency departments: A systematic review. Australas Emerg Care, 21, 111-120. 3. Schrier RW., Wang W., 2004. Acute renal failure and sepsis. N Engl J Med, 351, 159-169. 4. Tsiotou AG., Sakorafas GH., Anagnostopoulos G., Bramis J., 2005. Septic shock; current pathogenetic concepts from a clinical perspective. Med Sci Monit, 11, Ra76-85. 5. Lee DM., Hoffman WH., Carl GF., Khichi M., Cornwell PE., 2002. Lipid peroxidation and antioxidant vitamins prior to, during, and after correction of diabetic ketoacidosis. J Diabetes Complications, 16, 294-300. 6. Tok A., Sener E., Albayrak A., Cetin N., Polat B., Suleyman B., Akcay F., Suleyman H., 2012. Effect of mirtazapine on oxidative stress created in rat kidneys by ischemia-reperfusion. Ren Fail, 34, 103-110. 7. Ansari RA., Aswal BS., Chander R., Dhawan BN., Garg NK., Kapoor NK., Kulshreshtha DK., Mehdi H., Mehrotra BN., Patnaik GK., 1988. Hepatoprotective activity of kutkin-the iridoid glycoside mixture of Picrorhiza kurrooa. Indian J Med Res, 87, 401-404. 8. Erel O., 2005. A new automated colorimetric method for measuring total oxidant status. Clin Biochem, 38, 1103-1111. 9. Akdemir EFN., Tanyeli A., 2019. The Antioxidant Effect of Fraxin against Acute Organ Damage in Polymicrobial Sepsis Model induced by Cecal Ligation and Puncture. TJOS, 4, 22-29. 10. de Jong HK., van der Poll T., Wiersinga WJ., 2010. The systemic pro-inflammatory response in sepsis. J Innate Immun, 2, 422-430. 11. Gaut JP., Yeh GC., Tran HD., Byun J., Henderson JP., Richter GM., Brennan ML., Lusis AJ., Belaaouaj A., Hotchkiss RS., Heinecke JW., 2001. Neutrophils employ the myeloperoxidase system to generate antimicrobial brominating and chlorinating oxidants during sepsis. Proc Natl Acad Sci U S A, 98, 11961-11966. 12. Han Q., Yuan Q., Meng X., Huo J., Bao Y., Xie G. 2017. 6-Shogaol attenuates LPS-induced inflammation in BV2 microglia cells by activating PPAR-γ. Oncotarget, 8, 42001-42006. 13. Na JY., Song K., Lee JW., Kim S., Kwon J., 2016. Pretreatment of 6-shogaol attenuates oxidative stress and inflammation in middle cerebral artery occlusion-induced mice. Eur J Pharmacol, 788, 241-247. 14. Na JY., Song K., Lee JW., Kim S., Kwon J., 2016. 6-Shogaol has anti-amyloidogenic activity and ameliorates Alzheimer's disease via CysLT1R-mediated inhibition of cathepsin B. Biochem Biophys Res Commun, 477, 96-102. 15. Moon M., Kim HG., Choi JG., Oh H., Lee PK., Ha SK., Kim SY., Park Y., Huh Y., Oh MS., 2014. 6-Shogaol, an active constituent of ginger, attenuates neuroinflammation and cognitive deficits in animal models of dementia. Biochem Biophys Res Commun, 449, 8-13. 16. Akdemir EFN., Yildirim S., Kandemir FM., Tanyeli A., Küçükler S., Bahaeddin DM., 2019. Protective effects of gallic acid on doxorubicin-induced cardiotoxicity; an experimantal study. Arch Physiol Biochem, 26, 1-8. 17. Han SJ., Kim M., D'Agati VD., Lee HT., 2019. 6-Shogaol protects against ischemic acute kidney injury by modulating NF-κB and heme oxygenase-1 pathways. Am J Physiol Renal Physiol, 317, F743-F756. 18. Ohkawa H., Ohishi N., Yagi K., 1979. Assay for lipid peroxides in animal-tissues by thiobarbituric acid reaction. Anal Biochem, 95, 351-358. 19. Harma M., Harma M., Kocyigit A., Erel O., 2005. Increased DNA damage in patients with complete hydatidiform mole. Mutat Res, 583, 49-54. 20. Bradley PP., Priebat DA., Christensen RD., Rothstein G., 1982. Measurement of cutaneous inflammation: estimation of neutrophil content with an enzyme marker. J Invest Dermatol, 78, 206-209. 21. Sun Y., Oberley LW., Li Y., 1988. A simple method for clinical assay of superoxide-dismutase. Clin Chem, 34, 497-500. 22. Cecconi M., Evans L., Levy M., Rhodes A., 2018. Sepsis and septic shock. Lancet, 392, 75-87. 23. Xu G., Mo L., Wu C., Shen X., Dong H., Yu L., Pan P., Pan K., 2019. The miR-15a-5p-XIST-CUL3 regulatory axis is important for sepsis-induced acute kidney injury. Ren Fail, 41, 955-966. 24. Srisawat N., Lawsin L., Uchino S., Bellomo R., Kellum JA., 2010. Cost of acute renal replacement therapy in the intensive care unit: results from the beginning and ending supportive therapy for the kidney (BEST Kidney) study. Crit Care, 14, R46. 25. Rhodes A., Evans LE., Alhazzani W., Levy MM., Antonelli M., Ferrer R., Kumar A., Sevransky JE., Sprung CL., Nunnally ME., Rochwerg B., Rubenfeld GD., Angus DC., Annane D., Beale RJ., Bellinghan GJ., Bernard GR., Chiche JD., Coopersmith C., De Backer DP., French CJ., Fujishima S., Gerlach H., Hidalgo JL., Hollenberg SM., Jones AE., Karnad DR., Kleinpell RM., Koh Y., Lisboa TC., Machado FR., Marini JJ., Marshall JC., Mazuski JE., McIntyre LA., McLean AS., Mehta S., Moreno RP., Myburgh J., Navalesi P., Nishida O., Osborn TM., Perner A., Plunkett CM., Ranieri M., Schorr CA., Seckel MA., Seymour CW., Shieh L., Shukri KA., Simpson SQ., Singer M., Thompson BT., Townsend SR., Van der Poll T., Vincent JL., Wiersinga WJ., Zimmerman JL., Dellinger RP., 2017. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock. Intensive Care Med, 43, 304-377. 26. Zolali E., Hamishehkar H., Maleki-Dizaji N., Majidi Zolbanin N., Ghavimi H., Kouhsoltani M., Asgharian P., 2014. Selenium effect on oxidative stress factors in septic rats. Adv Pharm Bull, 4, 289-293. 27. Buras JA., Holzmann B., Sitkovsky M., 2005. Animal models of sepsis: setting the stage. Nat Rev Drug Discov, 4, 854-865. 28. Damas P., Ledoux D., Nys M., Vrindts Y., De Groote D., Franchimont P., Lamy M., 1992. Cytokine serum level during severe sepsis in human IL-6 as a marker of severity. Ann Surg, 215, 356-362. 29. De Jong HK., Van Der Poll T., Wiersinga WJ., 2010. The systemic pro-inflammatory response in sepsis. J Innate Immun, 2, 422-430. 30. Cakir M., Polat A., Tekin S., Vardi N., Taslidere E., Rumeysa DZ., Tanbek K., 2015. The effect of dexmedetomidine against oxidative and tubular damage induced by renal ischemia reperfusion in rats. Ren Fail, 37, 704-708. 31. Nie H., Xue X., Liu G., Guan G., Liu H., Sun L., Zhao L., Wang X., Chen Z., 2016. Nitro-oleic acid ameliorates oxygen and glucose deprivation/re-oxygenation triggered oxidative stress in renal tubular cells via activation of Nrf2 and suppression of NADPH oxidase. Free Radic Res, 50, 1200-1213. 32. Han HS., Kim KB., Jung JH., An IS., Kim YJ., An S., 2018. Anti-apoptotic, antioxidant and anti-aging effects of 6-shogaol on human dermal fibroblasts. Biomedical Dermatology, 2, 1-8. 33. Ma Q. 2013. Role of nrf2 in oxidative stress and toxicity. Annu Rev Pharmacol Toxicol, 53, 401-426. 34. Kadioglu E., Teksen Y., Kocak C., Kocak FE., 2019. Beneficial effects of bardoxolone methyl, an Nrf2 activator, on crush-related acute kidney injury in rats. Eur J Trauma Emerg Surg, 1-10. 35. Perkins ND., 2000. The Rel/NF-kappa B family: friend and foe. Trends Biochem Sci, 25, 434-440. 36. Brown KA., Brain SD., Pearson JD., Edgeworth JD., Lewis SM., Treacher DF., 2006. Neutrophils in development of multiple organ failure in sepsis. Lancet, 368, 157-169. 37. Cassatella MA., 1999. Neutrophil-derived proteins: selling cytokines by the pound. Adv Immunol, 73, 369-509. 38. Mortaz E., Alipoor SD., Adcock IM., Mumby S., Koenderman L., 2018. Update on Neutrophil Function in Severe Inflammation. Front Immunol, 9, 2171. 39. Lu TF., Yang TH., Zhong CP., Shen C., Lin WW., Gu GX., Xia Q., Xu N., 2018. Dual Effect of Hepatic Macrophages on Liver Ischemia and Reperfusion Injury during Liver Transplantation. Immune Netw, 18, e24. 40. Ozkanlar FA., Halıcı Z., Uyanık MH., 2016. Comparison of the therapeutic effects of antibiotic, steroid, and vitamin K during early sepsis in laboratory animals. Atatürk Üniversitesi Vet. Bil. Derg, 11, 13-21. 41. Wang CY., Hsieh MJ., Hsieh IC., Shie SS., Ho MY., Yeh JK., Tsai ML., Yang CH., Hung KC., Wang CC., Wen MS., 2016. CLOCK modulates survival and acute lung injury in mice with polymicrobial sepsis. Biochem Biophys Res Commun, 478, 935-941
Toplam 1 adet kaynakça vardır.
Ayrıntılar
| Birincil Dil | İngilizce |
|---|---|
| Konular | Sağlık Kurumları Yönetimi |
| Bölüm | Araştırma Makaleleri |
| Yazarlar | |
| Proje Numarası | Yok |
| Yayımlanma Tarihi | 31 Aralık 2020 |
| Yayımlandığı Sayı | Yıl 2020 Cilt: 15 Sayı: 3 |