Ellagik Asidin Çekal Ligasyon ve Delmeye Bağlı Akciğer Hasarı Üzerine Etkileri
Year 2020,
Volume: 15 Issue: 3, 223 - 230, 31.12.2020
Ersen Eraslan
,
Derya Güzel
,
Songül Doğanay
,
Mustafa Can Güler
,
Ayhan Tanyeli
,
Selim Çomaklı
Abstract
Ellagik asit, sıçanlarda çekal ligasyon ve delmeye (ÇLD) bağlı polimikrobiyal sepsis modelinin neden olduğu akciğer dokusu hasarı üzerinde incelendi. 24 Wistar Albino dişi sıçan 3 gruba ayrıldı: Grup I (sham), grup II (ÇLD) ve grup III (ÇLD + Ellagik asit 75 mg / kg). ÇLD modeli çekumun delinmesi ile gerçekleştirildi. Biyokimyasal ve immünohistokimyasal analizler yapıldı. Total oksidan kapasite, tümör nekroz faktör-α, interlökin-1β, malondialdehit ve miyeloperoksidaz aktivitesi arttı, ancak süperoksit dismütaz ve total antioksidan kapasite değerleri sham grubuyla karşılaştırıldığında ÇLD grubunda azaldı. Aksine, ellagik asit tedavi grubunda miyeloperoksidaz aktivitesi, total oksidan kapasite, tümör nekroz faktör-α, interlökin-1β, ve malondialdehit seviyeleri azalırken süperoksit dismütaz ve total antioksidan kapasite düzeyleri artmıştır. Kaspaz-3 ve LC3B immünopozitifliği ellagik asit grubunda azalırken, ÇLD grubunda sham grubuna göre anlamlı olarak artmıştır. Sonuç olarak ellagik asit, deneysel sıçanlarda ÇLD'nin neden olduğu akciğer hasarını önledi. Dolayısıyla ellagik asit, sepsisin neden olduğu akciğer dokusu hasarına karşı alternatif bir terapötik ajan olabilir.
Supporting Institution
Yok
References
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6. Zhou J., Fu Y., Liu K., Hou L., Zhang W., 2019. miR-206 regulates alveolar type II epithelial cell Cx43 expression in sepsis-induced acute lung injury. Exp Ther Med, 18, 296-304.
7. Störmann P., Becker N., Vollrath JT., Köhler K., Janicova A., Wutzler S., Hildebrand F., Marzi I., Relja B., 2019. Early local inhibition of Club Cell Protein 16 Following Chest Trauma Reduces Late Sepsis-Induced Acute Lung Injury. J Clin Med, 8, 896-901.
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9. Tanyeli A., Güzel D., 2019. Alliin mitigates Cecal Ligation Puncture (CLP)-induced lung injury through antioxidant and antiinflammatory effects. TJOS, 4, 46-59.
10. Tanyeli A., Guzel D., 2019. Investigation into the Biochemical Effects of Barbaloin on Renal Tissue in Cecal Ligation and Puncture-Induced Polymicrobial Sepsis Model in Rats. South Clin Ist Euras, 30, 285-9.
11. Lelubre C., Vincent JL., 2018. Mechanisms and treatment of organ failure in sepsis. Nat Rev Nephrol, 14, 417-27.
12. Gotts JE., Matthay MA., 2016. Sepsis: pathophysiology and clinical management. BMJ, 353, 1585-2005.
13. Kaymak C., Basar H., Sardas S., 2011. Reactive oxygen species (ROS) generation in sepsis. FABAD J Pharm Sci, 36, 41-47.
14. De Jong HK., Van Der Poll T., Wiersinga WJ., 2010. The systemic pro-inflammatory response in sepsis. J Innate Immun, 2, 422-430.
15. Li K., Yang J., Han X., 2016. Ketamine attenuates sepsis-induced acute lung injury via regulationof HMGB1-RAGE pathways. Int Immunopharmacol, 34, 114-128.
16. Derosa G., Maffioli P., Sahebkar A., 2016. Ellagic acid and its role in chronic diseases. Adv Exp Med Biol, 928, 473-479.
17. Zafrilla P., Ferreres F., Tomas-Barberan FA., 2001. Effect of processing and storage on the antioxidant ellagic acid derivatives and flavonoids of red raspberry (Rubus idaeus) jams. J Agric Food Chem, 49, 3651-3655.
18. Seeram NP., Zhang Y., McKeever R., Henning SM., Lee RP., Suchard M., Li Z., Chen S., Thames G., Zerlin A., Nguyen M., Wang D., Dreher M., Heber D., 2008. Pomegranate juice and extracts provide similar levels of plasma and urinary ellagitannin metabolites in human subjects. J Med Food, 11, 390-394.
19. Salem AM., Mohammaden TF., Ali MAM., Mohamed EA., Hasan HF., 2016. Ellagic and ferulic acids alleviate gamma radiation and aluminium chloride-induced oxidative damage. Life Sci, 160, 2-11.
20. Masamune A., Satoh M., Kikuta K., Suzuki N., Satoh K., Shimosegawa T., 2005. Ellagic acid blocks activation of pancreatic stellate cells. Biochem Pharmacol, 70, 869-878.
21. Favarin CD., Teixeira MM., Lemos de Andrade E., de Freitas Alves C., Lazo Chica JE., Sorgi CA., Faccioli LH., Rogerio AP., 2013. Anti-inflammatory effects of ellagic acid on acute lung injury induced by acid in mice. Mediators Inflamm, 2013, 1-13.
22. Ekinci AFN., Tanyeli A., 2019. The antioxidant effect of fraxin against acute organ damage in polymicrobial sepsis model induced cecal ligation and puncture. TJOS, 4, 22-29.
23. Ohkawa H., Ohishi N., Yagi K., 1979. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem, 95, 351-358.
24. Erel O., 2005. A new automated colorimetric method for measuring total oxidant status. Clin Biochem, 38, 1103-1111.
25. 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.
26. Sun Y., Oberley LW., Li Y., 1988. A simple method for clinical assay of superoxide dismutase. Clin Chem, 34, 497-500.
27. Lo S., Yuan SS., Hsu C., Cheng YJ., Chang YF., Hsueh HW., Lee PH., Hsieh YC., 2013. Lc3 over-expression improves survival and attenuates lung injury through increasing autophagosomal clearance in septic mice. Ann Surg, 257, 352-363.
28. Rittirsch D., Flierl MA., Ward PA., 2008. Harmful molecular mechanisms in sepsis. Nat Rev Immunol, 8, 776-787.
29. Deutschman CS., Tracey KJ., 2014. Sepsis: current dogma and new perspectives. Immunity, 40, 463-475.
30. Napolitano LM., 2018. Sepsis 2018: Definitions and guideline changes. Surg Infect (Larchmt), 19, 117-125.
31. Ware LB., 2006. Pathophysiology of acute lung injury and the acute respiratory distress syndrome. Semin Respir Crit Care Med, 27, 337-349.
32. Polat B., Cadirci E., Halici Z., Bayir Y., Unal D., Bilgin BC., Yuksel TN., Vancelik S., 2013. The protective effect of amiodarone in lung tissue of cecal ligation and puncture-induced septic rats: a perspective from inflammatory cytokine release and oxidative stress. Naunyn Schmiedebergs Arch Pharmacol, 386, 635-643.
33. Butt Y., Kurdowska A., Allen TC., 2016. Acute lung injury: A clinical and molecular review. Arch Pathol Lab Med, 140, 345-350.
34. Akpinar E., Halici Z., Cadirci E., Bayir Y., Karakus E., Calik M., Topcu A., Polat B., 2014. What is the role of renin inhibition during rat septic conditions: preventive effect of aliskiren on sepsis-induced lung injury. Naunyn Schmiedebergs Arch Pharmacol, 387, 969-978.
35. Guo RF., Ward PA., 2007. Role of oxidants in lung injury during sepsis. Antioxid Redox Signal, 9, 1991-2002.
36. Macdonald J., Galley HF., Webster NR., 2003. Oxidative stress and gene expression in sepsis. Br J Anaesth, 90, 221-232.
37. Gough DR., Cotter TG., 2011. Hydrogen peroxide: a Jekyll and Hyde signalling molecule. Cell Death Dis, 2, 213-221.
38. Halliwell B., Aeschbach R., Löliger J., Aruoma OI., 1995. The characterization of antioxidants. Food Chem Toxicol, 33, 601-617.
- 39. Keith ES., Powers JJ., 1965. Effect of phenolic acids and esters on respiration and reproduction of bacteria in urine. Appl Microbiol, 13, 308-313.
40. Cadirci E., Altunkaynak BZ., Halici Z., Odabasoglu F., Uyanik MH., Gundogdu C., Suleyman G., Halici M., Albayrak M., Unal B., 2010. Alpha-lipoic acid as a potential target for the treatment of lung injury caused by cecal ligation and puncture-induced sepsis model in rats. Shock, 33, 479-484.
41. Akdis M., Aab A., Altunbulakli C., Azkur K., Costa RA., Crameri R., Duan S., Eiwegger T., Eljaszewicz A., Ferstl R., Frei R., Garbani M., Globinska A., Hess L., Huitema C., Kubo T., Komlosi Z., Konieczna P., Kovacs N., Kucuksezer UC., Meyer N., Morita H., Olzhausen J., O'Mahony L., Pezer M., Prati M., Rebane A., Rhyner C., Rinaldi A., Sokolowska M., Stanic B., Sugita K., Treis A., Veen W., Wanke K., Wawrzyniak M., Wawrzyniak P., Wirz OF., Zakzuk JS., Akdis CA., 2016. Interleukins (from IL-1 to IL-38), interferons, transforming growth factor β, and TNF-α: Receptors, functions, and roles in diseases. J Allergy Clin Immunol, 138, 984-1010.
42. Li JY., Wu HX., Yang G., 2017. Pachymic acid improves survival and attenuates acute lung injury in septic rats induced by cecal ligation and puncture. Eur Rev Med Pharmacol Sci, 21, 1904-1910.
43. Schulte W., Bernhagen J., Bucala R., 2013. Cytokines in sepsis: potent immunoregulators and potential therapeutic targets-an updated view. Mediators Inflamm, 2013, 1-16.
44. Sadasivan S., Waghray A., Larner SF., Dunn WA., Hayes RL., Wang KK., 2006. Amino acid starvation induced autophagic cell death in PC-12 cells: evidence for activation of caspase-3 but not calpain-1. Apoptosis, 11, 1573-1582.
45. Jiang Y., Gao M., Wang W., Lang Y., Tong Z, Kangkai Wang K., Zhang H., Chen G., Liu M., Yao Y., Xiao X., 2015. Sinomenine hydrochloride protects against polymicrobial sepsis via autophagy. Int J Mol Sci, 16, 2559-2573.
46. Wan SX., Shi B., Lou XL., Liu JQ., Ma GG., Liang DY., Ma S., 2016. Ghrelin protects small intestinal epithelium against sepsis-induced injury by enhancing the autophagy of intestinal epithelial cells. Biomed Pharmacother, 83, 1315-1320.
47. Sirois I., Groleau J., Pallet N., Brassard N., Hamelin K., Londono I., Pshezhetsky AV., Bendayan M., Hébert MJ., 2012. Caspase activation regulates the extracellular export of autophagic vacuoles. Autophagy, 8, 927-37
The Effects of Ellagic Acid on Cecal Ligation and Puncture-Induced Lung Injury
Year 2020,
Volume: 15 Issue: 3, 223 - 230, 31.12.2020
Ersen Eraslan
,
Derya Güzel
,
Songül Doğanay
,
Mustafa Can Güler
,
Ayhan Tanyeli
,
Selim Çomaklı
Abstract
Ellagic acid was examined on lung tissue injury caused by cecal ligation and puncture (CLP)-induced polymicrobial sepsis model in rats. 24 Wistar Albino female rats were allocated to 3 groups as: Group I (Sham), group II (CLP), and group III (CLP+ Ellagic acid 75 mg/kg). The CLP model was made by drilling the cecum. Biochemical and immunohistochemical analyzes were performed. Total oxidant status, tumor necrosis factor-α, interleukin-1β, malondialdehyde, and myeloperoxidase activity elevated, but superoxide dismutase and total antioxidant status valued declined in the CLP group compared to the sham group. On the contrary, superoxide dismutase and total antioxidant status levels increased. In contrast, myeloperoxidase activity, total oxidant status, tumor necrosis factor-α, interleukin-1β, and malondialdehyde levels decreased in the Ellagic acid treatment group. Caspase-3 and microtubule-associated protein light chain-3B immunopositivity increased significantly in the CLP group compared to the sham group while diminishing in the Ellagic acid group. In conclusion, Ellagic acid prevented CLP-induced lung injury in experimental rats. Thus, Ellagic acid may be an alternative therapeutic agent against lung tissue injury induced by sepsis.
References
- 1. Bhan C., Dipankar P., Chakraborty P., Sarangi PP., 2016. Role of cellular events in the pathophysiology of sepsis. Inflamm Res, 65, 853-68.
2. Mayr FB., Yende S., Angus DC., 2014. Epidemiology of severe sepsis. Virulence, 5, 4-11.
3. Angus DC., Wax RS., 2001. Epidemiology of sepsis: an update. Crit Care Med, 29, 109-116.
4. Troeger C., Blacker B., Khalil IA., Rao PC., Cao J., Zimsen SRM., Albertson SB., Deshpande A., Farag T., Abebe Z., Adetifa IMO., Adhikari TB., Akibu M., Al Lami FH., Al-Eyadhy A., Alvis-Guzman N., Amare AT., Amoako YA., Antonio CAT., Aremu O., Asfaw ET., Asgedom SW., Atey TM., Attia EF., Avokpaho EFGA., Ayele HT., Ayuk TB., Balakrishnan K., Barac A., Bassat Q., Behzadifar M., Behzadifar M., Bhaumik S., Bhutta ZA., Bijani A., Brauer M., Brown A., Camargos PAM., Castañeda-Orjuela CA., Colombara D., Conti S., Dadi AF., Dandona L., Dandona R., Phuc Do H., Dubljanin E., Edessa D., Elkout H., Endries AY., Fijabi DO., Foreman KJ., Forouzanfar MH., Fullman N., Garcia-Basteiro AL., Gessner BD., Gething PW., Gupta R., Gupta T., Hailu GB., Hassen HY., Hedayati MT., Heidari M., Hibstu DT., Horita N., Ilesanmi OS., Jakovljevic MB., Jamal AA., Kahsay A., Kasaeian A., Kassa DH., Khader YS., Khan EA., Khan MN., Khang YH, Kim YJ., Kissoon N., Knibbs LD, Kochhar S., Koul PA., Kumar GA, Lodha R., El Razek HMA., Malta DC., Mathew JL., Mengistu TD., Mezgebe HB., Mohammad KA., Mohammed MA., Momeniha F., Murthy S., Nguyen CT., Nielsen KR., Ningrum DNA., Nirayo YL., Oren E., Ortiz JR., Pa M., Postma MJ., Qorbani M., Quansah R., Rai RK., Rana SM., Ranabhat CL., Ray SE., Rezai MS., Ruhago GM., Safiri., Salomon JA., Sartorius B., Savic M., Sawhney M., She J., Sheikh A., Shiferaw MS., Shigematsu M., Singh JA., Somayaji R., Stanaway JD., Sufiyan MB., Taffere GR., Temsah MH., Thompson MJ., Tobe-Gai R., Topor-Madry R., Tran BX., Tran TT., Tuem KB., Ukwaja KN., Vollset SE., Walson JL, Weldegebreal F., Werdecker A., West TE., Yonemoto N., Zaki MS., Zhou L., Zodpey S., Vos W., Naghavi M, Lim SS., Mokdad AL., Murray CJL., Hay SI., Reiner Jr RC., 2016. Estimates of the global, regional, and national morbidity, mortality, and aetiologies of lower respiratory infections in 195 countries, 1990-2016: a systematic analysis for the Global Burden of Disease Study. Lancet Infect Dis, 18, 1191-210.
5. Chen X., Wang T., Song L., Liu X., 2019. Activation of multiple Toll-like receptors serves different roles in sepsis-induced acute lung injury. Exp Ther Med, 18, 443-450.
6. Zhou J., Fu Y., Liu K., Hou L., Zhang W., 2019. miR-206 regulates alveolar type II epithelial cell Cx43 expression in sepsis-induced acute lung injury. Exp Ther Med, 18, 296-304.
7. Störmann P., Becker N., Vollrath JT., Köhler K., Janicova A., Wutzler S., Hildebrand F., Marzi I., Relja B., 2019. Early local inhibition of Club Cell Protein 16 Following Chest Trauma Reduces Late Sepsis-Induced Acute Lung Injury. J Clin Med, 8, 896-901.
8. Güzel D., Tanyeli A., 2018. Inhibition of NADPH oxidase attenuates sepsis induced acute lung oxidative damage in rats. J Cell Neurosci Oxid Stress, 10, 714.
9. Tanyeli A., Güzel D., 2019. Alliin mitigates Cecal Ligation Puncture (CLP)-induced lung injury through antioxidant and antiinflammatory effects. TJOS, 4, 46-59.
10. Tanyeli A., Guzel D., 2019. Investigation into the Biochemical Effects of Barbaloin on Renal Tissue in Cecal Ligation and Puncture-Induced Polymicrobial Sepsis Model in Rats. South Clin Ist Euras, 30, 285-9.
11. Lelubre C., Vincent JL., 2018. Mechanisms and treatment of organ failure in sepsis. Nat Rev Nephrol, 14, 417-27.
12. Gotts JE., Matthay MA., 2016. Sepsis: pathophysiology and clinical management. BMJ, 353, 1585-2005.
13. Kaymak C., Basar H., Sardas S., 2011. Reactive oxygen species (ROS) generation in sepsis. FABAD J Pharm Sci, 36, 41-47.
14. De Jong HK., Van Der Poll T., Wiersinga WJ., 2010. The systemic pro-inflammatory response in sepsis. J Innate Immun, 2, 422-430.
15. Li K., Yang J., Han X., 2016. Ketamine attenuates sepsis-induced acute lung injury via regulationof HMGB1-RAGE pathways. Int Immunopharmacol, 34, 114-128.
16. Derosa G., Maffioli P., Sahebkar A., 2016. Ellagic acid and its role in chronic diseases. Adv Exp Med Biol, 928, 473-479.
17. Zafrilla P., Ferreres F., Tomas-Barberan FA., 2001. Effect of processing and storage on the antioxidant ellagic acid derivatives and flavonoids of red raspberry (Rubus idaeus) jams. J Agric Food Chem, 49, 3651-3655.
18. Seeram NP., Zhang Y., McKeever R., Henning SM., Lee RP., Suchard M., Li Z., Chen S., Thames G., Zerlin A., Nguyen M., Wang D., Dreher M., Heber D., 2008. Pomegranate juice and extracts provide similar levels of plasma and urinary ellagitannin metabolites in human subjects. J Med Food, 11, 390-394.
19. Salem AM., Mohammaden TF., Ali MAM., Mohamed EA., Hasan HF., 2016. Ellagic and ferulic acids alleviate gamma radiation and aluminium chloride-induced oxidative damage. Life Sci, 160, 2-11.
20. Masamune A., Satoh M., Kikuta K., Suzuki N., Satoh K., Shimosegawa T., 2005. Ellagic acid blocks activation of pancreatic stellate cells. Biochem Pharmacol, 70, 869-878.
21. Favarin CD., Teixeira MM., Lemos de Andrade E., de Freitas Alves C., Lazo Chica JE., Sorgi CA., Faccioli LH., Rogerio AP., 2013. Anti-inflammatory effects of ellagic acid on acute lung injury induced by acid in mice. Mediators Inflamm, 2013, 1-13.
22. Ekinci AFN., Tanyeli A., 2019. The antioxidant effect of fraxin against acute organ damage in polymicrobial sepsis model induced cecal ligation and puncture. TJOS, 4, 22-29.
23. Ohkawa H., Ohishi N., Yagi K., 1979. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem, 95, 351-358.
24. Erel O., 2005. A new automated colorimetric method for measuring total oxidant status. Clin Biochem, 38, 1103-1111.
25. 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.
26. Sun Y., Oberley LW., Li Y., 1988. A simple method for clinical assay of superoxide dismutase. Clin Chem, 34, 497-500.
27. Lo S., Yuan SS., Hsu C., Cheng YJ., Chang YF., Hsueh HW., Lee PH., Hsieh YC., 2013. Lc3 over-expression improves survival and attenuates lung injury through increasing autophagosomal clearance in septic mice. Ann Surg, 257, 352-363.
28. Rittirsch D., Flierl MA., Ward PA., 2008. Harmful molecular mechanisms in sepsis. Nat Rev Immunol, 8, 776-787.
29. Deutschman CS., Tracey KJ., 2014. Sepsis: current dogma and new perspectives. Immunity, 40, 463-475.
30. Napolitano LM., 2018. Sepsis 2018: Definitions and guideline changes. Surg Infect (Larchmt), 19, 117-125.
31. Ware LB., 2006. Pathophysiology of acute lung injury and the acute respiratory distress syndrome. Semin Respir Crit Care Med, 27, 337-349.
32. Polat B., Cadirci E., Halici Z., Bayir Y., Unal D., Bilgin BC., Yuksel TN., Vancelik S., 2013. The protective effect of amiodarone in lung tissue of cecal ligation and puncture-induced septic rats: a perspective from inflammatory cytokine release and oxidative stress. Naunyn Schmiedebergs Arch Pharmacol, 386, 635-643.
33. Butt Y., Kurdowska A., Allen TC., 2016. Acute lung injury: A clinical and molecular review. Arch Pathol Lab Med, 140, 345-350.
34. Akpinar E., Halici Z., Cadirci E., Bayir Y., Karakus E., Calik M., Topcu A., Polat B., 2014. What is the role of renin inhibition during rat septic conditions: preventive effect of aliskiren on sepsis-induced lung injury. Naunyn Schmiedebergs Arch Pharmacol, 387, 969-978.
35. Guo RF., Ward PA., 2007. Role of oxidants in lung injury during sepsis. Antioxid Redox Signal, 9, 1991-2002.
36. Macdonald J., Galley HF., Webster NR., 2003. Oxidative stress and gene expression in sepsis. Br J Anaesth, 90, 221-232.
37. Gough DR., Cotter TG., 2011. Hydrogen peroxide: a Jekyll and Hyde signalling molecule. Cell Death Dis, 2, 213-221.
38. Halliwell B., Aeschbach R., Löliger J., Aruoma OI., 1995. The characterization of antioxidants. Food Chem Toxicol, 33, 601-617.
- 39. Keith ES., Powers JJ., 1965. Effect of phenolic acids and esters on respiration and reproduction of bacteria in urine. Appl Microbiol, 13, 308-313.
40. Cadirci E., Altunkaynak BZ., Halici Z., Odabasoglu F., Uyanik MH., Gundogdu C., Suleyman G., Halici M., Albayrak M., Unal B., 2010. Alpha-lipoic acid as a potential target for the treatment of lung injury caused by cecal ligation and puncture-induced sepsis model in rats. Shock, 33, 479-484.
41. Akdis M., Aab A., Altunbulakli C., Azkur K., Costa RA., Crameri R., Duan S., Eiwegger T., Eljaszewicz A., Ferstl R., Frei R., Garbani M., Globinska A., Hess L., Huitema C., Kubo T., Komlosi Z., Konieczna P., Kovacs N., Kucuksezer UC., Meyer N., Morita H., Olzhausen J., O'Mahony L., Pezer M., Prati M., Rebane A., Rhyner C., Rinaldi A., Sokolowska M., Stanic B., Sugita K., Treis A., Veen W., Wanke K., Wawrzyniak M., Wawrzyniak P., Wirz OF., Zakzuk JS., Akdis CA., 2016. Interleukins (from IL-1 to IL-38), interferons, transforming growth factor β, and TNF-α: Receptors, functions, and roles in diseases. J Allergy Clin Immunol, 138, 984-1010.
42. Li JY., Wu HX., Yang G., 2017. Pachymic acid improves survival and attenuates acute lung injury in septic rats induced by cecal ligation and puncture. Eur Rev Med Pharmacol Sci, 21, 1904-1910.
43. Schulte W., Bernhagen J., Bucala R., 2013. Cytokines in sepsis: potent immunoregulators and potential therapeutic targets-an updated view. Mediators Inflamm, 2013, 1-16.
44. Sadasivan S., Waghray A., Larner SF., Dunn WA., Hayes RL., Wang KK., 2006. Amino acid starvation induced autophagic cell death in PC-12 cells: evidence for activation of caspase-3 but not calpain-1. Apoptosis, 11, 1573-1582.
45. Jiang Y., Gao M., Wang W., Lang Y., Tong Z, Kangkai Wang K., Zhang H., Chen G., Liu M., Yao Y., Xiao X., 2015. Sinomenine hydrochloride protects against polymicrobial sepsis via autophagy. Int J Mol Sci, 16, 2559-2573.
46. Wan SX., Shi B., Lou XL., Liu JQ., Ma GG., Liang DY., Ma S., 2016. Ghrelin protects small intestinal epithelium against sepsis-induced injury by enhancing the autophagy of intestinal epithelial cells. Biomed Pharmacother, 83, 1315-1320.
47. Sirois I., Groleau J., Pallet N., Brassard N., Hamelin K., Londono I., Pshezhetsky AV., Bendayan M., Hébert MJ., 2012. Caspase activation regulates the extracellular export of autophagic vacuoles. Autophagy, 8, 927-37