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Klorokuin Endoplazmik Retikulum Stresini ve Enflamasyonu İnhibe Ederek Sıçanlarda Adriamisin Uyarılı Kardiyotoksisiteyi Engeller

Yıl 2020, Cilt: 77 Sayı: 4, 459 - 466, 01.12.2020

Öz

Amaç: Adriamisin ADR kanser türlerinde kullanılan kemoterapötik bir ilaç olarak bilinmektedir. ADR uyarılı kardiyomiyopati toksik özelliğinden dolayı ilacın kullanımını zorlaştırmaktadır. ADR uyarılı kardiyotoksisitede enflamasyon ve endoplazmik retikulum stresi ERs artmaktadır. Pek çok kanser türünde kullanılan kemoterapötik ilaç olan ADR’nin yol açtığı kardiyotoksisiteye karşı sıtma ilacı olan klorokuin CLQ kullanımının ERs ve enflamasyon üzerinden koruyucu etkilerinin araştırılması amaçlandı. Yöntem: Sıçanlar rastgele 4 gruba ayrıldı: Kontrol grubu n = 8 dışındakilere, CLQ n = 8 günde 50 mg/kg intraperitoneal i.p. , ADR n = 8 2 mg/kg i.p. olarak her 3 günde bir, ADR + CLQ grubuna da n = 8 2mg/kg i.p. ADR + 50 mg/kg i.p. CLQ uygulandı. Deney toplam 30 gün sürdü. Deneyin sonunda, sıçanlar sakrifiye edildi ve kalp dokuları inceleme için hayvanlardan çıkarıldı. Kalp dokularındaki histopatolojik değişiklikler değerlendirildi ve ERs’yi belirlemek için Glukoz düzenleyici protein GRP78 antikoru ve enflamasyon için tümör nekroz faktörü-α TNF-α antikoru ile immün boyama yapıldı. Fotoğraflar Olympus BX53 mikroskobu ile çekildi analiz edildi.Bulgular: ADR grubunun kontrol grubuna kıyasla histopatolojik bozulma gösterdiğini ve CLQ tedavisinin ADR tarafından indüklenen bu hasarı iyileştirdiği gözlemlendi. ADR grubunda GRP78 ve TNF-α immünoreaktivitesinde kontrol grubuna göre artış vardı p

Kaynakça

  • Chung CK, Garcia-Couce J, Campos Y, Kralisch D, Bierau K, Chan A, et al. Doxorubicin loaded poloxamer thermosensitive hydrogels: chemical, pharmacological and biological evaluation. Molecules, 2020;25(9).
  • Jang YJ, Lee D, Hossain MA, Aravinthan A, Kang CW, Kim NS, et al. Korean Red Ginseng enhances cardiac hemodynamics on doxorubicin-induced toxicity in rats. J Ginseng Res, 2020;44(3):483-9.
  • Minotti G, Menna P, Salvatorelli E, Cairo G, Gianni L. Anthracyclines: molecular advances and pharmacologic developments in antitumor activity and cardiotoxicity. Pharmacol Rev, 2004;56(2):185- 229.
  • Zhang Q, Wu G, Guo S, Liu Y, Liu Z. Effects of tristetraprolin on doxorubicin (adriamycin)- induced experimental kidney injury through inhibiting IL-13/STAT6 signal pathway. Am J Trans Res, 2020;12(4):1203-21.
  • Wali AF, Rashid S, Rashid SM, Ansari MA, Khan MR, Haq N, et al. Naringenin Regulates Doxorubicin- Induced Liver Dysfunction: Impact on Oxidative Stress and Inflammation. Plants, 2020;9(4).
  • Ozturk E, Kaymak E, Akin AT, Karabulut D, Unsal HM, Yakan B. Thymoquinone is a protective agent that reduces the negative effects of doxorubicin in rat testis. Hum Exp Toxicol, 2020:960327120924108.
  • Yang HL, Hsieh PL, Hung CH, Cheng HC, Chou WC, Chu PM, et al. Early moderate intensity aerobic exercise intervention prevents doxorubicin-caused cardiac dysfunction through inhibition of cardiac fibrosis and inflammation. Cancers, 2020;12(5).
  • Tadokoro T, Ikeda M, Ide T, Deguchi H, Ikeda S, Okabe K, et al. Mitochondria-dependent ferroptosis plays a pivotal role in doxorubicin cardiotoxicity. JCI Insight, 2020;5(9).
  • Chatterjee K, Zhang J, Honbo N, Karliner JS. Doxorubicin cardiomyopathy. Cardiology, 2010;115(2):155-62.
  • Hu J, Wu Q, Wang Z, Hong J, Chen R, Li B, et al. Inhibition of CACNA1H attenuates doxorubicin-induced acute cardiotoxicity by affecting endoplasmic reticulum stress. Biomed Pharmacother, 2019;120:109475.
  • Sishi BJ, Loos B, van Rooyen J, Engelbrecht AM. Doxorubicin induces protein ubiquitination and inhibits proteasome activity during cardiotoxicity. Toxicol, 2013;309:23-9.
  • Tscheschner H, Meinhardt E, Schlegel P, Jungmann A, Lehmann LH, Muller OJ, et al. CaMKII activation participates in doxorubicin cardiotoxicity and is attenuated by moderate GRP78 overexpression. PloS One, 2019;14(4):e0215992.
  • Lan Y, Wang Y, Huang K, Zeng Q. Heat shock protein 22 attenuates doxorubicin-induced cardiotoxicity via regulating inflammation and apoptosis. Front pharmacol, 2020;11:257.
  • Bin Jardan YA, Ansari MA, Raish M, Alkharfy KM, Ahad A, Al-Jenoobi FI, et al. Sinapic acid ameliorates oxidative stress, inflammation, and apoptosis in acute doxorubicin-induced cardiotoxicity via the NF-kappaB-mediated pathway. BioMed Res Int, 2020;2020:3921796.
  • Hu TY, Frieman M, Wolfram J. Insights from nanomedicine into chloroquine efficacy against COVID-19. Nat Nanotechnol, 2020;15(4):247-9.
  • Askanase AD, Khalili L, Buyon JP. Thoughts on COVID-19 and autoimmune diseases. Lupus Sci Med, 2020;7(1):e000396.
  • Zhan F, Zhao G, Li X, Yang S, Yang W, Zhou S, et al. Inositol-requiring enzyme 1 alpha endoribonuclease specific inhibitor STF-083010 protects the liver from thioacetamide-induced oxidative stress, inflammation and injury by triggering hepatocyte autophagy. Int Immunopharmacol, 2019;73:261-9.
  • Shivakumar P, Rani MU, Reddy AG, Anjaneyulu Y. A study on the toxic effects of Doxorubicin on the histology of certain organs. Toxicol Int, 2012;19(3):241-4.
  • Long L, Yang X, Southwood M, Lu J, Marciniak SJ, Dunmore BJ, et al. Chloroquine prevents progression hypertension via inhibition of autophagy and lysosomal bone morphogenetic protein type II receptor degradation. Circ Res, 2013;112(8):1159- 70. pulmonary
  • Oztürk Küp F, Koçak B, Akin At, Doğanyiğit İ, Okan A, Kaymak E, et al. The effect of biosynthetic silver nanoparticles against intestinal toxicity caused by Lipopolysaccharide (LPS). Turk Hij Den Biyol Derg, 2020;77(3):333-42.
  • Karabulut D, Ulusoy HB, Kaymak E, Sonmez MF. Therapeutic effects of pentoxifylline on diabetic heart tissue via NOS. Anatol J Cardiol, 2016;16(5):310-5.
  • Sönmez MF, Ozdemir Ş, Guzel M, Kaymak E. The ameliorative effects of vinpocetine on apoptosis and HSP-70 expression in testicular torsion in rats. Biotech Histochem, 2017;92(2):92-9.
  • Sharma A, Parikh M, Shah H, Gandhi T. Modulation of Nrf2 by quercetin in doxorubicin-treated rats. Heliyon, 2020;6(4):e03803.
  • Gammella E, Maccarinelli F, Buratti P, Recalcati S, Cairo G. The role of iron in anthracycline cardiotoxicity. Front Pharmacol, 2014;5:25.
  • Sandamali JAN, Hewawasam RP, Jayatilaka K, Mudduwa LKB. Cardioprotective potential of murraya koenigii (L.) Spreng. leaf extract against Doxorubicin-induced cardiotoxicity in rats. Evid Based Complement Alternat Med, 2020;2020:6023737.
  • Liao D, Xiang D, Dang R, Xu P, Wang J, Han W, et al. Neuroprotective effects of dl-3-n-Butylphthalide against Doxorubicin-induced neuroinflammation, oxidative stress, endoplasmic reticulum stress, and behavioral changes. Oxid Med Cell Longev, 2018;2018:9125601.
  • Chen RC, Sun GB, Ye JX, Wang J, Zhang MD, Sun XB. Salvianolic acid B attenuates doxorubicin- induced ER stress by inhibiting TRPC3 and TRPC6 mediated Ca(2+) overload in rat cardiomyocytes. Toxicol Lett, 2017;276:21-30.
  • Wang Z, Wang M, Liu J, Ye J, Jiang H, Xu Y, et al. Inhibition of TRPA1 attenuates Doxorubicin- induced acute cardiotoxicity by suppressing oxidative stress, the inflammatory response, and endoplasmic reticulum stress. Oxid Med Cell Longev, 2018;2018:5179468.
  • Yayi H, Yeda X, Huaxin W, Yang W, Qian S, Zhongyuan X. Toll-like receptor 7 involves the injury in acute kidney ischemia/reperfusion of STZ-induced diabetic rats. Acta Cir Bras, 2016;31(7):448-55.
  • Todorovic Z, Medic B, Basta-Jovanovic G, Radojevic Skodric S, Stojanovic R, Rovcanin B, et al. Acute pretreatment with chloroquine attenuates renal I/R injury in rats. PloS One, 2014;9(3):e92673-e.
  • Mubagwa K. Cardiac effects and toxicity of chloroquine: a short update. Int J Antimicrob Agents, 2020;56(2):106057.
  • Costedoat-Chalumeau N, Hulot J-S, Amoura Z, Leroux G, Lechat P, Funck-Brentano C, et al. Heart conduction disorders related to antimalarials toxicity: an analysis of electrocardiograms in 85 patients treated with hydroxychloroquine for connective tissue diseases. Rheumatology, 2007;46(5):808-10.

Chloroquine Inhibits Adriamycin-Induced Cardiotoxicity İn Rats By Inhibiting Endoplasmic Reticulum Stress And Inflammation

Yıl 2020, Cilt: 77 Sayı: 4, 459 - 466, 01.12.2020

Öz

Objective: Adriamycin ADR is known as a chemotherapeutic drug used in cancer types. ADRinduced cardiomyopathy makes it difficult to use the drug due to its toxic properties. Inflammation and ER stress increase in ADR-induced cardiotoxicity. The aim of this study was to investigate the protective effects of chloroquine CLQ , a malaria medication used in many types of cancer, against the cardiotoxicity caused by ADR on endoplasmic reticulum stress and inflammation.Methods: Rats were randomly divided into 4 groups: Control n = 8 , CLQ n = 8 50 mg/kg intraperitoneal i.p. daily, ADR n = 8 2 mg/kg i.p. every 3 days, ADR + CLQ n = 8 2mg/kg i.p. ADR + 50 mg/kg i.p. CLQ. The experiment lasted a total of 30 days. At the end of the experiment, the rats were sacrificed and the heart tissues were removed from the animals for examination. Histopathological changes in the heart tissues were evaluated and immune staining was performed with Glucose-regulated protein 78 GRP78 antibody and tumor necrosis factor-α TNF-α antibody for inflammation to determine endoplasmic reticulum stress. Photos were taken with Olympus BX53 microscope and analyzed.Adriamisin ADR pek çok kanser tedavisinde kullanılan kuvvetli bir terapötik maddedir 1 . ADR solid ve hemotopoetik tümörlerin tedavisinde kullanılan antrasiklin bir ilaçtır 2 . İlaç kanser hücrelerinde bu özelliğini topoizomeraz II ile DNA hasarının başlatılması ve apoptozisi gibi süreçlerle yapmaktadır 3 . İlaç klinikte kullanılmasına rağmen yan etkieri de bulunmaktadır. Kanser hastalarında ADR kullanımı arasında böbrek, karaciğer, testis ve kalp gibi önemli organlarda hasara yol açmaktadır . ADR uyarılı kardiyomiyopati toksik özelliğinden dolayı ilacın kullanımını sınırlandırmaktadır 8 . ADR uyarılı kardiyotoksisiteye birçok mekanizma karışmaktadır. ADR kardiyomiyositlerde geri dönüşümsüz hasar oluşturabilmektedir. Sistolik ve diastolik fonksiyon kaybına yol açabilmektedir. Kalp yetmezliğine götürmektedir 8, 9 . ADR vücuda girdiğine Results: We observed that the ADR group showed histopathological impairment compared to the Control group and that CLQ treatment improved this ADRinduced damage. In the ADR group, there was an increase in GRP78 and TNF-α immunoreactivity compared to the control group p

Kaynakça

  • Chung CK, Garcia-Couce J, Campos Y, Kralisch D, Bierau K, Chan A, et al. Doxorubicin loaded poloxamer thermosensitive hydrogels: chemical, pharmacological and biological evaluation. Molecules, 2020;25(9).
  • Jang YJ, Lee D, Hossain MA, Aravinthan A, Kang CW, Kim NS, et al. Korean Red Ginseng enhances cardiac hemodynamics on doxorubicin-induced toxicity in rats. J Ginseng Res, 2020;44(3):483-9.
  • Minotti G, Menna P, Salvatorelli E, Cairo G, Gianni L. Anthracyclines: molecular advances and pharmacologic developments in antitumor activity and cardiotoxicity. Pharmacol Rev, 2004;56(2):185- 229.
  • Zhang Q, Wu G, Guo S, Liu Y, Liu Z. Effects of tristetraprolin on doxorubicin (adriamycin)- induced experimental kidney injury through inhibiting IL-13/STAT6 signal pathway. Am J Trans Res, 2020;12(4):1203-21.
  • Wali AF, Rashid S, Rashid SM, Ansari MA, Khan MR, Haq N, et al. Naringenin Regulates Doxorubicin- Induced Liver Dysfunction: Impact on Oxidative Stress and Inflammation. Plants, 2020;9(4).
  • Ozturk E, Kaymak E, Akin AT, Karabulut D, Unsal HM, Yakan B. Thymoquinone is a protective agent that reduces the negative effects of doxorubicin in rat testis. Hum Exp Toxicol, 2020:960327120924108.
  • Yang HL, Hsieh PL, Hung CH, Cheng HC, Chou WC, Chu PM, et al. Early moderate intensity aerobic exercise intervention prevents doxorubicin-caused cardiac dysfunction through inhibition of cardiac fibrosis and inflammation. Cancers, 2020;12(5).
  • Tadokoro T, Ikeda M, Ide T, Deguchi H, Ikeda S, Okabe K, et al. Mitochondria-dependent ferroptosis plays a pivotal role in doxorubicin cardiotoxicity. JCI Insight, 2020;5(9).
  • Chatterjee K, Zhang J, Honbo N, Karliner JS. Doxorubicin cardiomyopathy. Cardiology, 2010;115(2):155-62.
  • Hu J, Wu Q, Wang Z, Hong J, Chen R, Li B, et al. Inhibition of CACNA1H attenuates doxorubicin-induced acute cardiotoxicity by affecting endoplasmic reticulum stress. Biomed Pharmacother, 2019;120:109475.
  • Sishi BJ, Loos B, van Rooyen J, Engelbrecht AM. Doxorubicin induces protein ubiquitination and inhibits proteasome activity during cardiotoxicity. Toxicol, 2013;309:23-9.
  • Tscheschner H, Meinhardt E, Schlegel P, Jungmann A, Lehmann LH, Muller OJ, et al. CaMKII activation participates in doxorubicin cardiotoxicity and is attenuated by moderate GRP78 overexpression. PloS One, 2019;14(4):e0215992.
  • Lan Y, Wang Y, Huang K, Zeng Q. Heat shock protein 22 attenuates doxorubicin-induced cardiotoxicity via regulating inflammation and apoptosis. Front pharmacol, 2020;11:257.
  • Bin Jardan YA, Ansari MA, Raish M, Alkharfy KM, Ahad A, Al-Jenoobi FI, et al. Sinapic acid ameliorates oxidative stress, inflammation, and apoptosis in acute doxorubicin-induced cardiotoxicity via the NF-kappaB-mediated pathway. BioMed Res Int, 2020;2020:3921796.
  • Hu TY, Frieman M, Wolfram J. Insights from nanomedicine into chloroquine efficacy against COVID-19. Nat Nanotechnol, 2020;15(4):247-9.
  • Askanase AD, Khalili L, Buyon JP. Thoughts on COVID-19 and autoimmune diseases. Lupus Sci Med, 2020;7(1):e000396.
  • Zhan F, Zhao G, Li X, Yang S, Yang W, Zhou S, et al. Inositol-requiring enzyme 1 alpha endoribonuclease specific inhibitor STF-083010 protects the liver from thioacetamide-induced oxidative stress, inflammation and injury by triggering hepatocyte autophagy. Int Immunopharmacol, 2019;73:261-9.
  • Shivakumar P, Rani MU, Reddy AG, Anjaneyulu Y. A study on the toxic effects of Doxorubicin on the histology of certain organs. Toxicol Int, 2012;19(3):241-4.
  • Long L, Yang X, Southwood M, Lu J, Marciniak SJ, Dunmore BJ, et al. Chloroquine prevents progression hypertension via inhibition of autophagy and lysosomal bone morphogenetic protein type II receptor degradation. Circ Res, 2013;112(8):1159- 70. pulmonary
  • Oztürk Küp F, Koçak B, Akin At, Doğanyiğit İ, Okan A, Kaymak E, et al. The effect of biosynthetic silver nanoparticles against intestinal toxicity caused by Lipopolysaccharide (LPS). Turk Hij Den Biyol Derg, 2020;77(3):333-42.
  • Karabulut D, Ulusoy HB, Kaymak E, Sonmez MF. Therapeutic effects of pentoxifylline on diabetic heart tissue via NOS. Anatol J Cardiol, 2016;16(5):310-5.
  • Sönmez MF, Ozdemir Ş, Guzel M, Kaymak E. The ameliorative effects of vinpocetine on apoptosis and HSP-70 expression in testicular torsion in rats. Biotech Histochem, 2017;92(2):92-9.
  • Sharma A, Parikh M, Shah H, Gandhi T. Modulation of Nrf2 by quercetin in doxorubicin-treated rats. Heliyon, 2020;6(4):e03803.
  • Gammella E, Maccarinelli F, Buratti P, Recalcati S, Cairo G. The role of iron in anthracycline cardiotoxicity. Front Pharmacol, 2014;5:25.
  • Sandamali JAN, Hewawasam RP, Jayatilaka K, Mudduwa LKB. Cardioprotective potential of murraya koenigii (L.) Spreng. leaf extract against Doxorubicin-induced cardiotoxicity in rats. Evid Based Complement Alternat Med, 2020;2020:6023737.
  • Liao D, Xiang D, Dang R, Xu P, Wang J, Han W, et al. Neuroprotective effects of dl-3-n-Butylphthalide against Doxorubicin-induced neuroinflammation, oxidative stress, endoplasmic reticulum stress, and behavioral changes. Oxid Med Cell Longev, 2018;2018:9125601.
  • Chen RC, Sun GB, Ye JX, Wang J, Zhang MD, Sun XB. Salvianolic acid B attenuates doxorubicin- induced ER stress by inhibiting TRPC3 and TRPC6 mediated Ca(2+) overload in rat cardiomyocytes. Toxicol Lett, 2017;276:21-30.
  • Wang Z, Wang M, Liu J, Ye J, Jiang H, Xu Y, et al. Inhibition of TRPA1 attenuates Doxorubicin- induced acute cardiotoxicity by suppressing oxidative stress, the inflammatory response, and endoplasmic reticulum stress. Oxid Med Cell Longev, 2018;2018:5179468.
  • Yayi H, Yeda X, Huaxin W, Yang W, Qian S, Zhongyuan X. Toll-like receptor 7 involves the injury in acute kidney ischemia/reperfusion of STZ-induced diabetic rats. Acta Cir Bras, 2016;31(7):448-55.
  • Todorovic Z, Medic B, Basta-Jovanovic G, Radojevic Skodric S, Stojanovic R, Rovcanin B, et al. Acute pretreatment with chloroquine attenuates renal I/R injury in rats. PloS One, 2014;9(3):e92673-e.
  • Mubagwa K. Cardiac effects and toxicity of chloroquine: a short update. Int J Antimicrob Agents, 2020;56(2):106057.
  • Costedoat-Chalumeau N, Hulot J-S, Amoura Z, Leroux G, Lechat P, Funck-Brentano C, et al. Heart conduction disorders related to antimalarials toxicity: an analysis of electrocardiograms in 85 patients treated with hydroxychloroquine for connective tissue diseases. Rheumatology, 2007;46(5):808-10.
Toplam 32 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Bölüm Araştırma Makalesi
Yazarlar

Emin Kaymak Bu kişi benim

Ali Tuğrul Akın Bu kişi benim

Emel Öztürk Bu kişi benim

Tayfun Ceylan Bu kişi benim

Nurhan Kuloğlu Bu kişi benim

Derya Karabulut Bu kişi benim

Birkan Yakan Bu kişi benim

Yayımlanma Tarihi 1 Aralık 2020
Yayımlandığı Sayı Yıl 2020 Cilt: 77 Sayı: 4

Kaynak Göster

APA Kaymak, E., Akın, A. T., Öztürk, E., Ceylan, T., vd. (2020). Chloroquine Inhibits Adriamycin-Induced Cardiotoxicity İn Rats By Inhibiting Endoplasmic Reticulum Stress And Inflammation. Türk Hijyen Ve Deneysel Biyoloji Dergisi, 77(4), 459-466.
AMA Kaymak E, Akın AT, Öztürk E, Ceylan T, Kuloğlu N, Karabulut D, Yakan B. Chloroquine Inhibits Adriamycin-Induced Cardiotoxicity İn Rats By Inhibiting Endoplasmic Reticulum Stress And Inflammation. Turk Hij Den Biyol Derg. Aralık 2020;77(4):459-466.
Chicago Kaymak, Emin, Ali Tuğrul Akın, Emel Öztürk, Tayfun Ceylan, Nurhan Kuloğlu, Derya Karabulut, ve Birkan Yakan. “Chloroquine Inhibits Adriamycin-Induced Cardiotoxicity İn Rats By Inhibiting Endoplasmic Reticulum Stress And Inflammation”. Türk Hijyen Ve Deneysel Biyoloji Dergisi 77, sy. 4 (Aralık 2020): 459-66.
EndNote Kaymak E, Akın AT, Öztürk E, Ceylan T, Kuloğlu N, Karabulut D, Yakan B (01 Aralık 2020) Chloroquine Inhibits Adriamycin-Induced Cardiotoxicity İn Rats By Inhibiting Endoplasmic Reticulum Stress And Inflammation. Türk Hijyen ve Deneysel Biyoloji Dergisi 77 4 459–466.
IEEE E. Kaymak, A. T. Akın, E. Öztürk, T. Ceylan, N. Kuloğlu, D. Karabulut, ve B. Yakan, “Chloroquine Inhibits Adriamycin-Induced Cardiotoxicity İn Rats By Inhibiting Endoplasmic Reticulum Stress And Inflammation”, Turk Hij Den Biyol Derg, c. 77, sy. 4, ss. 459–466, 2020.
ISNAD Kaymak, Emin vd. “Chloroquine Inhibits Adriamycin-Induced Cardiotoxicity İn Rats By Inhibiting Endoplasmic Reticulum Stress And Inflammation”. Türk Hijyen ve Deneysel Biyoloji Dergisi 77/4 (Aralık 2020), 459-466.
JAMA Kaymak E, Akın AT, Öztürk E, Ceylan T, Kuloğlu N, Karabulut D, Yakan B. Chloroquine Inhibits Adriamycin-Induced Cardiotoxicity İn Rats By Inhibiting Endoplasmic Reticulum Stress And Inflammation. Turk Hij Den Biyol Derg. 2020;77:459–466.
MLA Kaymak, Emin vd. “Chloroquine Inhibits Adriamycin-Induced Cardiotoxicity İn Rats By Inhibiting Endoplasmic Reticulum Stress And Inflammation”. Türk Hijyen Ve Deneysel Biyoloji Dergisi, c. 77, sy. 4, 2020, ss. 459-66.
Vancouver Kaymak E, Akın AT, Öztürk E, Ceylan T, Kuloğlu N, Karabulut D, Yakan B. Chloroquine Inhibits Adriamycin-Induced Cardiotoxicity İn Rats By Inhibiting Endoplasmic Reticulum Stress And Inflammation. Turk Hij Den Biyol Derg. 2020;77(4):459-66.