Thymol reduces the lipopolysaccharide-induced acute kidney inflammation by modulating lysosomal stress

Yalçın Erzurumlu; Hatice Kübra Doğan; Deniz Çataklı

Araştırma Makalesi

Thymol reduces the lipopolysaccharide-induced acute kidney inflammation by modulating lysosomal stress

Yıl 2023, Cilt: 27 Sayı: 2, 722 - 732, 27.06.2025

Yalçın Erzurumlu , Hatice Kübra Doğan , Deniz Çataklı

Öz

Inflammation-induced overexpression of cytokines can lead to cell death by caspase-dependent or
independent signaling pathways. Numerous natural products are used to suppress/re-modulate inflammation.
Phenolic monoterpene thymol is widely used in cosmetics and for medical purposes. It has been shown that thymol
regulates the anti-inflammatory, antioxidant and anti-apoptotic responses in lipopolysaccharide (LPS)-induced in vitro
and in vivo models. However, there is still a need to investigate the molecular mechanism of inflammation and the
detailed regulatory roles of thymol on inflammation-dependent signal mechanisms. In the present study, the possible
protective effects of thymol on inflammation-mediated lysosomal stress in the LPS-induced acute kidney inflammation
model were investigated on HEK293 cells. To mimic the inflammation in HEK293 cells, LPS was applied to the cells for
24 h. Following, cells were treated with various doses of thymol and total protein was isolated from the cells.
Inflammation-associated Interleukin-6 (IL-6), tumor necrosis factor-⍺ (TNF-⍺), nuclear factor kappa B (Nf-κB) and
phospho-Nf-κB protein levels, autophagy-related Beclin-1, autophagy-related 5 (Atg5), p62/SQSTM1 and microtubule-
associated protein 1A/1B-light chain 3 (LC3-I/II), ubiquitin proteosome system-associated polyubiquitin, cell death-
associated caspase-3 and poly (ADP-ribose) polymerase (PARP-1) protein levels were examined by immunoblotting.
We find that LPS-induced acute inflammation caused the suppressing of autophagic flux and reducing degradation of
polyubiquitinated proteins. Thymol treatment markedly reversed the suppression of autophagy and stacking of poly-
ubiquitinated protein by LPS. Also, LPS-induced acute inflammation did not cause caspase activation, it caused an
increase in lysosomal stress-related PARP-1 cleavage pattern and thymol administration efficiently reduced PARP-1
cleavage. Our results suggested that LPS-induced acute inflammation triggers blockage of autophagic flux and thymol
has a protective role against LPS-induced lysosomal stress.

Anahtar Kelimeler

Autophagy, inflammation, lysosomal stress, thymol

Kaynakça

Balkwill F, Mantovani A. Inflammation and cancer: back to Virchow? Lancet. 2001; 357(9255):539–45. https://doi.org/10.1016/S0140-6736(00)04046-0
Aggarwal BB. Nuclear factor-kappaB: the enemy within. Cancer Cell. 2004; 6(3):203–8. https://doi.org/10.1016/j.ccr.2004.09.003
Dolcet X, Llobet D, Pallares J, Matias-Guiu X. NF-kB in development and progression of human cancer. Virchows Archiv. 2005;446(5),475–82. https://doi.org/10.1007/s00428-005-1264-9
Hayden MS, Ghosh S. Signaling to NF-kappaB. Genes Dev. 2004;18(18):2195–224. https://doi.org/10.1101/gad.1228704
Fehrenbacher N, Bastholm L, Kirkegaard-Sørensen T, Rafn B, Bøttzauw T, Nielsen C, Weber E, Shirasawa S, Kallunki T, Jaattela M. Sensitization to the Lysosomal Cell Death Pathway by Oncogene-Induced Down-regulation of Lysosome-Associated Membrane Proteins 1 and 2. Cancer Research. 2008;68: 6623–33. https://doi.org/10.1158/0008-5472.CAN-08-0463
Karch J, Schips TG, Maliken BD, Brody MJ, Sargent MA, Kanisicak O, Molkentin JD. Autophagic cell death is dependent on lysosomal membrane permeability through Bax and Bak. eLife. 2017;6:e30543. https://doi.org/10.7554/eLife.30543
Boya P, Kroemer G. Lysosomal membrane permeabilization in cell death. Oncogene. 2008;27(50): 6434–6451. https://doi.org/10.1038/onc.2008.310
Wu Y, Sun Y, Dong X, Chen J, Wang Z, Chen J, Dong G. The Synergism of PGN, LTA and LPS in Inducing Transcriptome Changes, Inflammatory Responses and a Decrease in Lactation as Well as the Associated Epigenetic Mechanisms in Bovine Mammary Epithelial Cells. Toxins. 2020;12(6): 387. https://doi.org/10.3390/toxins12060387
Cao X, Jin Y, Zhang H, Yu L, Bao X, Li F, Xu Y. The Anti-inflammatory Effects of 4-((5-Bromo-3-chloro-2- hydroxybenzyl) amino)-2-hydroxybenzoic Acid in Lipopolysaccharide-Activated Primary Microglial Cells. Inflammation. 2018;41(2):530–40. https://doi.org/10.1007/s10753-017-0709-z
Rahmani AH, Al Zohairy MA, Aly SM, Khan MA. Curcumin: a potential candidate in prevention of cancer via modulation of molecular pathways. Biomed Res Int. 2014; 2014:761608. https://doi.org/10.1155/2014/761608
Akbar S. Thymus vulgaris L. (Lamiaceae) Handbook of 200 Medicinal Plants. 2020, p. 1795–810. http://doi.org/10.1007/978-3-030-16807-0_185
Basch E, Ulbricht C, Hammerness P, Bevins A, Sollars D. Thyme (Thymus vulgaris L.), Thymol. Vol. 4, Journal of Herbal Pharmacotherapy. 2004;4(1):49-67. https://doi.org/10.1080/J157v04n01_07
Marchese A, Orhan IE, Daglia M, Barbieri R, Di Lorenzo A, Nabavi SF, Gortzi O, Izadi M, Nabavi SM. Antibacterial and antifungal activities of thymol: A brief review of the literature. Food Chem. 2016; 210:402–14. https://doi.org/10.1016/j.foodchem.2016.04.111
Rustaiyan A, Masoudi S, Monfared A, Kamalinejad M, Lajevardi T, Sedaghat S, Yari M. Volatile constituents of three Thymus species grown wild in Iran. Planta Med. 2000;66(2):197–8. https://doi.org/10.1055/s-0029-1243136
Soliman KM, Badeaa RI. Effect of oil extracted from some medicinal plants on different mycotoxigenic fungi. Food Chem Toxicol. 2002;40(11):1669–75. https://doi.org/10.1016/s0278-6915(02)00120-5
Lee SP, Buber MT, Yang Q, Cerne R, Cortés RY, Sprous DG, Bryant RW. Thymol and related alkyl phenols activate the hTRPA1 channel. Br J Pharmacol. 2008;153(8):1739–49. https://doi.org/10.1038/bjp.2008.85
Yang J, Hooper WC, Phillips DJ, Talkington DF. Interleukin-1beta responses to Mycoplasma pneumoniae infection are cell-type specific. Microb Pathog. 2003;34(1):17–25. https://doi.org/10.1016/S0882-4010(02)00190-0
Yao L, Hou G, Wang L, Zuo XS, Liu Z. Protective effects of thymol on LPS-induced acute lung injury in mice. Microbial Pathogenesis. 2018;116: 8–12. https://doi.org/10.1016/j.micpath.2017.12.065
El-Sayed EM, Abd-Allah AR, Mansour AM, El-Arabey AA. Thymol and carvacrol prevent cisplatin-induced nephrotoxicity by abrogation of oxidative stress, inflammation, and apoptosis in rats. J Biochem Mol Toxicol. 2015;29(4):165–72. https://doi.org/10.1002/jbt.21681
Elbe H, Yigitturk G, Cavusoglu T, Uyanikgil Y, Ozturk F. Apoptotic effects of thymol, a novel monoterpene phenol, on different types of cancer. Bratisl Lek Listy. 2020;121(2):122–8. https://doi.org/10.4149/BLL_2020_016
Yücel G, Zhao Z, El-Battrawy I, Lan H, Lang S, Li X, Buljubasic F, Zimmermann WH, Cyganek L, Utikal J, Ravens U, Wieland T, Borggrefe M, Zhou XB, Akin I. Lipopolysaccharides induced inflammatory responses and electrophysiological dysfunctions in human-induced pluripotent stem cell derived cardiomyocytes. Sci Rep. 2017;7(1):1–13. https://doi.org/10.1038/s41598-017-03147-4
Tucureanu MM, Rebleanu D, Constantinescu CA, Deleanu M, Voicu G, Butoi E, Calin M, Manduteanu I. Lipopolysaccharide-induced inflammation in monocytes/macrophages is blocked by liposomal delivery of G- protein inhibitor. Int J Nanomedicine. 2018; 13:63–76. https://doi.org/10.2147/IJN.S150918
Liu X, Yin S, Chen Y, Wu Y, Zheng W, Dong H, Bai Y, Qin Y, Li J, Feng S, Zhao P. LPS‑induced proinflammatory cytokine expression in human airway epithelial cells and macrophages via NF‑κB, STAT3 or AP‑1 activation. Mol Med Rep. 2018;17(4):5484–91. https://doi.org/10.3892/mmr.2018.8542
Liu T, Zhang L, Joo D, Sun SC. NF-κB signaling in inflammation. Signal Transduct Target Ther. 2017;2:17023. https://doi.org/10.1038/sigtrans.2017.23
Klionsky DJ, Emr SD. Autophagy as a Regulated Pathway of Cellular Degradation. Science.2000;290(5497):1717-1721. http://doi.org/10.1126/science.290.5497.1717
Nandi D, Tahiliani P, Kumar A, Chandu D. The ubiquitin-proteasome system. J Biosci. 2006;31(1):137–55. https://doi.org/10.1007/BF02705243
Korolchuk VI, Mansilla A, Menzies FM, Rubinsztein DC. Autophagy inhibition compromises degradation of ubiquitin-proteasome pathway substrates. Mol Cell. 2009;33(4):517–27. https://doi.org/10.1016/j.molcel.2009.01.021
Pohl C, Dikic I. Cellular quality control by the ubiquitin-proteasome system and autophagy. Science. 2019;366(6467):818–822. http://doi.org/10.1126/science.aax3769
Wang XJ, Yu J, Wong SH, Cheng ASL, Chan FKL, Ng SSM, Cho CH, Sung JJY, Wu WKK. A novel crosstalk between two major protein degradation systems: regulation of proteasomal activity by autophagy. Autophagy. 2013;9(10):1500–8. https://doi.org/10.4161/auto.25573
Liu WJ, Ye L, Huang WF, Guo LJ, Xu ZG, Wu HL, Yang C, Liu HF. p62 links the autophagy pathway and the ubiqutin- proteasome system upon ubiquitinated protein degradation. Cell Mol Biol Lett. 2016; 21:29. https://doi.org/10.1186/s11658-016-0031-z
Nicoletti VG, Stella AMG. Role of PARP Under Stress Conditions: Cell Death or Protection?. Neurochemical Research. 2003;28(2):187–94. http://doi.org/10.1023/a:1022316914492
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Maiden MJ, Otto S, Brealey JK, Finnis ME, Chapman MJ, Kuchel TR, Nash CH, Edwards J, Bellomo R. Structure and Function of the Kidney in Septic Shock. A Prospective Controlled Experimental Study. Am J Respir Crit Care Med. 2016;194(6):692–700. https://doi.org/10.1164/rccm.201511-2285OC
Wang Z, Holthoff JH, Seely KA, Pathak E, Spencer HJ 3rd, Gokden N, Mayeux PR. Development of oxidative stress in the peritubular capillary microenvironment mediates sepsis-induced renal microcirculatory failure and acute kidney injury. Am J Pathol. 2012;180(2):505–16. https://doi.org/10.1016/j.ajpath.2011.10.011
Ronco C, Bellomo R, Kellum JA. Acute kidney injury. Lancet. 2019;394(10212):1949–64. https://doi.org/10.1016/S0140-6736(19)32563-2
Kliger AS, Foley RN, Goldfarb DS, Goldstein SL, Johansen K, Singh A, Szczech L. KDOQI US commentary on the 2012 KDIGO Clinical Practice Guideline for Anemia in CKD. Am J Kidney Dis. 2013;62(5):849–59. https://doi.org/10.1053/j.ajkd.2013.06.008
Hoste EAJ. Epidemiology of Acute Kidney Injury in Critically Ill Patients. In Critical Care Nephrology. 2019, p. 81– 85. https://doi.org/10.1016/B978-0-323-44942-7.00013-3
Chauhan AK, Jakhar R, Paul S, Kang SC. Potentiation of macrophage activity by thymol through augmenting phagocytosis. Int Immunopharmacol. 2014;18(2):340–6. https://doi.org/10.1016/j.intimp.2013.11.025
Negishi H, Fujita Y, Yanai H, Sakaguchi S, Ouyang X, Shinohara M, Takayanagi H, Ohba Y, Taniguchi T, Honda K. Evidence for licensing of IFN-gamma-induced IFN regulatory factor 1 transcription factor by MyD88 in Toll-like receptor-dependent gene induction program. Proc Natl Acad Sci U S A. 2006; 103(41):15136–41. https://doi.org/10.1073/pnas.0607181103
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Yıl 2023, Cilt: 27 Sayı: 2, 722 - 732, 27.06.2025

Yalçın Erzurumlu , Hatice Kübra Doğan , Deniz Çataklı

Öz

Kaynakça

Balkwill F, Mantovani A. Inflammation and cancer: back to Virchow? Lancet. 2001; 357(9255):539–45. https://doi.org/10.1016/S0140-6736(00)04046-0
Aggarwal BB. Nuclear factor-kappaB: the enemy within. Cancer Cell. 2004; 6(3):203–8. https://doi.org/10.1016/j.ccr.2004.09.003
Dolcet X, Llobet D, Pallares J, Matias-Guiu X. NF-kB in development and progression of human cancer. Virchows Archiv. 2005;446(5),475–82. https://doi.org/10.1007/s00428-005-1264-9
Hayden MS, Ghosh S. Signaling to NF-kappaB. Genes Dev. 2004;18(18):2195–224. https://doi.org/10.1101/gad.1228704
Fehrenbacher N, Bastholm L, Kirkegaard-Sørensen T, Rafn B, Bøttzauw T, Nielsen C, Weber E, Shirasawa S, Kallunki T, Jaattela M. Sensitization to the Lysosomal Cell Death Pathway by Oncogene-Induced Down-regulation of Lysosome-Associated Membrane Proteins 1 and 2. Cancer Research. 2008;68: 6623–33. https://doi.org/10.1158/0008-5472.CAN-08-0463
Karch J, Schips TG, Maliken BD, Brody MJ, Sargent MA, Kanisicak O, Molkentin JD. Autophagic cell death is dependent on lysosomal membrane permeability through Bax and Bak. eLife. 2017;6:e30543. https://doi.org/10.7554/eLife.30543
Boya P, Kroemer G. Lysosomal membrane permeabilization in cell death. Oncogene. 2008;27(50): 6434–6451. https://doi.org/10.1038/onc.2008.310
Wu Y, Sun Y, Dong X, Chen J, Wang Z, Chen J, Dong G. The Synergism of PGN, LTA and LPS in Inducing Transcriptome Changes, Inflammatory Responses and a Decrease in Lactation as Well as the Associated Epigenetic Mechanisms in Bovine Mammary Epithelial Cells. Toxins. 2020;12(6): 387. https://doi.org/10.3390/toxins12060387
Cao X, Jin Y, Zhang H, Yu L, Bao X, Li F, Xu Y. The Anti-inflammatory Effects of 4-((5-Bromo-3-chloro-2- hydroxybenzyl) amino)-2-hydroxybenzoic Acid in Lipopolysaccharide-Activated Primary Microglial Cells. Inflammation. 2018;41(2):530–40. https://doi.org/10.1007/s10753-017-0709-z
Rahmani AH, Al Zohairy MA, Aly SM, Khan MA. Curcumin: a potential candidate in prevention of cancer via modulation of molecular pathways. Biomed Res Int. 2014; 2014:761608. https://doi.org/10.1155/2014/761608
Akbar S. Thymus vulgaris L. (Lamiaceae) Handbook of 200 Medicinal Plants. 2020, p. 1795–810. http://doi.org/10.1007/978-3-030-16807-0_185
Basch E, Ulbricht C, Hammerness P, Bevins A, Sollars D. Thyme (Thymus vulgaris L.), Thymol. Vol. 4, Journal of Herbal Pharmacotherapy. 2004;4(1):49-67. https://doi.org/10.1080/J157v04n01_07
Marchese A, Orhan IE, Daglia M, Barbieri R, Di Lorenzo A, Nabavi SF, Gortzi O, Izadi M, Nabavi SM. Antibacterial and antifungal activities of thymol: A brief review of the literature. Food Chem. 2016; 210:402–14. https://doi.org/10.1016/j.foodchem.2016.04.111
Rustaiyan A, Masoudi S, Monfared A, Kamalinejad M, Lajevardi T, Sedaghat S, Yari M. Volatile constituents of three Thymus species grown wild in Iran. Planta Med. 2000;66(2):197–8. https://doi.org/10.1055/s-0029-1243136
Soliman KM, Badeaa RI. Effect of oil extracted from some medicinal plants on different mycotoxigenic fungi. Food Chem Toxicol. 2002;40(11):1669–75. https://doi.org/10.1016/s0278-6915(02)00120-5
Lee SP, Buber MT, Yang Q, Cerne R, Cortés RY, Sprous DG, Bryant RW. Thymol and related alkyl phenols activate the hTRPA1 channel. Br J Pharmacol. 2008;153(8):1739–49. https://doi.org/10.1038/bjp.2008.85
Yang J, Hooper WC, Phillips DJ, Talkington DF. Interleukin-1beta responses to Mycoplasma pneumoniae infection are cell-type specific. Microb Pathog. 2003;34(1):17–25. https://doi.org/10.1016/S0882-4010(02)00190-0
Yao L, Hou G, Wang L, Zuo XS, Liu Z. Protective effects of thymol on LPS-induced acute lung injury in mice. Microbial Pathogenesis. 2018;116: 8–12. https://doi.org/10.1016/j.micpath.2017.12.065
El-Sayed EM, Abd-Allah AR, Mansour AM, El-Arabey AA. Thymol and carvacrol prevent cisplatin-induced nephrotoxicity by abrogation of oxidative stress, inflammation, and apoptosis in rats. J Biochem Mol Toxicol. 2015;29(4):165–72. https://doi.org/10.1002/jbt.21681
Elbe H, Yigitturk G, Cavusoglu T, Uyanikgil Y, Ozturk F. Apoptotic effects of thymol, a novel monoterpene phenol, on different types of cancer. Bratisl Lek Listy. 2020;121(2):122–8. https://doi.org/10.4149/BLL_2020_016
Yücel G, Zhao Z, El-Battrawy I, Lan H, Lang S, Li X, Buljubasic F, Zimmermann WH, Cyganek L, Utikal J, Ravens U, Wieland T, Borggrefe M, Zhou XB, Akin I. Lipopolysaccharides induced inflammatory responses and electrophysiological dysfunctions in human-induced pluripotent stem cell derived cardiomyocytes. Sci Rep. 2017;7(1):1–13. https://doi.org/10.1038/s41598-017-03147-4
Tucureanu MM, Rebleanu D, Constantinescu CA, Deleanu M, Voicu G, Butoi E, Calin M, Manduteanu I. Lipopolysaccharide-induced inflammation in monocytes/macrophages is blocked by liposomal delivery of G- protein inhibitor. Int J Nanomedicine. 2018; 13:63–76. https://doi.org/10.2147/IJN.S150918
Liu X, Yin S, Chen Y, Wu Y, Zheng W, Dong H, Bai Y, Qin Y, Li J, Feng S, Zhao P. LPS‑induced proinflammatory cytokine expression in human airway epithelial cells and macrophages via NF‑κB, STAT3 or AP‑1 activation. Mol Med Rep. 2018;17(4):5484–91. https://doi.org/10.3892/mmr.2018.8542
Liu T, Zhang L, Joo D, Sun SC. NF-κB signaling in inflammation. Signal Transduct Target Ther. 2017;2:17023. https://doi.org/10.1038/sigtrans.2017.23
Klionsky DJ, Emr SD. Autophagy as a Regulated Pathway of Cellular Degradation. Science.2000;290(5497):1717-1721. http://doi.org/10.1126/science.290.5497.1717
Nandi D, Tahiliani P, Kumar A, Chandu D. The ubiquitin-proteasome system. J Biosci. 2006;31(1):137–55. https://doi.org/10.1007/BF02705243
Korolchuk VI, Mansilla A, Menzies FM, Rubinsztein DC. Autophagy inhibition compromises degradation of ubiquitin-proteasome pathway substrates. Mol Cell. 2009;33(4):517–27. https://doi.org/10.1016/j.molcel.2009.01.021
Pohl C, Dikic I. Cellular quality control by the ubiquitin-proteasome system and autophagy. Science. 2019;366(6467):818–822. http://doi.org/10.1126/science.aax3769
Wang XJ, Yu J, Wong SH, Cheng ASL, Chan FKL, Ng SSM, Cho CH, Sung JJY, Wu WKK. A novel crosstalk between two major protein degradation systems: regulation of proteasomal activity by autophagy. Autophagy. 2013;9(10):1500–8. https://doi.org/10.4161/auto.25573
Liu WJ, Ye L, Huang WF, Guo LJ, Xu ZG, Wu HL, Yang C, Liu HF. p62 links the autophagy pathway and the ubiqutin- proteasome system upon ubiquitinated protein degradation. Cell Mol Biol Lett. 2016; 21:29. https://doi.org/10.1186/s11658-016-0031-z
Nicoletti VG, Stella AMG. Role of PARP Under Stress Conditions: Cell Death or Protection?. Neurochemical Research. 2003;28(2):187–94. http://doi.org/10.1023/a:1022316914492
Fernandes-Alnemri T, Litwack G, Alnemri ES. CPP32, a novel human apoptotic protein with homology to Caenorhabditis elegans cell death protein Ced-3 and mammalian interleukin-1 beta-converting enzyme. J Biol Chem. 1994; 269(49):30761–4. https://doi.org/10.1016/s0021-9258(18)47344-9
Maiden MJ, Otto S, Brealey JK, Finnis ME, Chapman MJ, Kuchel TR, Nash CH, Edwards J, Bellomo R. Structure and Function of the Kidney in Septic Shock. A Prospective Controlled Experimental Study. Am J Respir Crit Care Med. 2016;194(6):692–700. https://doi.org/10.1164/rccm.201511-2285OC
Wang Z, Holthoff JH, Seely KA, Pathak E, Spencer HJ 3rd, Gokden N, Mayeux PR. Development of oxidative stress in the peritubular capillary microenvironment mediates sepsis-induced renal microcirculatory failure and acute kidney injury. Am J Pathol. 2012;180(2):505–16. https://doi.org/10.1016/j.ajpath.2011.10.011
Ronco C, Bellomo R, Kellum JA. Acute kidney injury. Lancet. 2019;394(10212):1949–64. https://doi.org/10.1016/S0140-6736(19)32563-2
Kliger AS, Foley RN, Goldfarb DS, Goldstein SL, Johansen K, Singh A, Szczech L. KDOQI US commentary on the 2012 KDIGO Clinical Practice Guideline for Anemia in CKD. Am J Kidney Dis. 2013;62(5):849–59. https://doi.org/10.1053/j.ajkd.2013.06.008
Hoste EAJ. Epidemiology of Acute Kidney Injury in Critically Ill Patients. In Critical Care Nephrology. 2019, p. 81– 85. https://doi.org/10.1016/B978-0-323-44942-7.00013-3
Chauhan AK, Jakhar R, Paul S, Kang SC. Potentiation of macrophage activity by thymol through augmenting phagocytosis. Int Immunopharmacol. 2014;18(2):340–6. https://doi.org/10.1016/j.intimp.2013.11.025
Negishi H, Fujita Y, Yanai H, Sakaguchi S, Ouyang X, Shinohara M, Takayanagi H, Ohba Y, Taniguchi T, Honda K. Evidence for licensing of IFN-gamma-induced IFN regulatory factor 1 transcription factor by MyD88 in Toll-like receptor-dependent gene induction program. Proc Natl Acad Sci U S A. 2006; 103(41):15136–41. https://doi.org/10.1073/pnas.0607181103
Sharif O, Bolshakov VN, Raines S, Newham P, Perkins ND. Transcriptional profiling of the LPS induced NF-kappaB response in macrophages. BMC Immunol. 2007; 8:1. https://doi.org/10.1186/1471-2172-8-1
Akira S, Hirano T, Taga T, Kishimoto T. Biology of multifunctional cytokines: IL 6 and related molecules (IL 1 and TNF). The FASEB Journal. 1990;4: 2860–2867. https://doi.org/10.1096/fasebj.4.11.2199284
Hochrainer K, Racchumi G, Anrather J. Site-specific phosphorylation of the p65 protein subunit mediates selective gene expression by differential NF-κB and RNA polymerase II promoter recruitment. J Biol Chem. 2013;288(1):285– 93. https://doi.org/10.1074/jbc.M112.385625
Anrather J, Racchumi G, Iadecola C. cis-acting, element-specific transcriptional activity of differentially phosphorylated nuclear factor-kappa B. J Biol Chem. 2005;280(1):244–52. https://doi.org/10.1074/jbc.M409344200
Wu H, Jiang K, Yin N, Ma X, Zhao G, Qiu C, Deng G. Thymol mitigates lipopolysaccharide-induced endometritis by regulating the TLR4- and ROS-mediated NF-κB signaling pathways. Oncotarget. 2017;8(12):20042–55. https://doi.org/10.18632/oncotarget.15373
Qian M, Fang X, Wang X. Autophagy and inflammation. Clinical and Translational Medicine. 2017;6(1):1-11. http://doi.org/10.1186/s40169-017-0154-5
Deretic V, Saitoh T, Akira S. Autophagy in infection, inflammation and immunity. Nat Rev Immunol. 2013;13(10):722–37. https://doi.org/10.1038/nri3532
Ding WX, Ni HM, Gao W, Yoshimori T, Stolz DB, Ron D, Yin XM. Linking of autophagy to ubiquitin-proteasome system is important for the regulation of endoplasmic reticulum stress and cell viability. Am J Pathol. 2007;171(2):513– 24. https://doi.org/10.2353/ajpath.2007.070188
Chaitanya GV, Alexander JS, Babu PP. PARP-1 cleavage fragments: signatures of cell-death proteases in neurodegeneration. Cell Commun Signal. 2010; 8:31. https://doi.org/10.1186/1478-811X-8-31
Artal-Sanz M, Samara C, Syntichaki P, Tavernarakis N. Lysosomal biogenesis and function is critical for necrotic cell death in Caenorhabditis elegans. J Cell Biol. 2006; 173(2):231–9. https://doi.org/10.1083/jcb.200511103
IIvanova S, Repnik U, Boji L, Petelin A, Turk V, Turk B. Lysosomes in apoptosis. Methods Enzymol. 2008;442:183-99. https://doi.org/10.1016/S0076-6879(08)01409-2
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Toplam 54 adet kaynakça vardır.

Ayrıntılar

Birincil Dil	İngilizce
Konular	Tıbbi Farmakoloji
Bölüm	Articles
Yazarlar	Yalçın Erzurumlu 0000-0001-6835-4436 Hatice Kübra Doğan 0000-0002-6061-1300 Deniz Çataklı 0000-0001-7327-5396
Yayımlanma Tarihi	27 Haziran 2025
Yayımlandığı Sayı	Yıl 2023 Cilt: 27 Sayı: 2

Kaynak Göster

APA	Erzurumlu, Y., Doğan, H. K., & Çataklı, D. (2025). Thymol reduces the lipopolysaccharide-induced acute kidney inflammation by modulating lysosomal stress. Journal of Research in Pharmacy, 27(2), 722-732.
AMA	Erzurumlu Y, Doğan HK, Çataklı D. Thymol reduces the lipopolysaccharide-induced acute kidney inflammation by modulating lysosomal stress. J. Res. Pharm. Haziran 2025;27(2):722-732.
Chicago	Erzurumlu, Yalçın, Hatice Kübra Doğan, ve Deniz Çataklı. “Thymol Reduces the Lipopolysaccharide-Induced Acute Kidney Inflammation by Modulating Lysosomal Stress”. Journal of Research in Pharmacy 27, sy. 2 (Haziran 2025): 722-32.
EndNote	Erzurumlu Y, Doğan HK, Çataklı D (01 Haziran 2025) Thymol reduces the lipopolysaccharide-induced acute kidney inflammation by modulating lysosomal stress. Journal of Research in Pharmacy 27 2 722–732.
IEEE	Y. Erzurumlu, H. K. Doğan, ve D. Çataklı, “Thymol reduces the lipopolysaccharide-induced acute kidney inflammation by modulating lysosomal stress”, J. Res. Pharm., c. 27, sy. 2, ss. 722–732, 2025.
ISNAD	Erzurumlu, Yalçın vd. “Thymol Reduces the Lipopolysaccharide-Induced Acute Kidney Inflammation by Modulating Lysosomal Stress”. Journal of Research in Pharmacy 27/2 (Haziran 2025), 722-732.
JAMA	Erzurumlu Y, Doğan HK, Çataklı D. Thymol reduces the lipopolysaccharide-induced acute kidney inflammation by modulating lysosomal stress. J. Res. Pharm. 2025;27:722–732.
MLA	Erzurumlu, Yalçın vd. “Thymol Reduces the Lipopolysaccharide-Induced Acute Kidney Inflammation by Modulating Lysosomal Stress”. Journal of Research in Pharmacy, c. 27, sy. 2, 2025, ss. 722-3.
Vancouver	Erzurumlu Y, Doğan HK, Çataklı D. Thymol reduces the lipopolysaccharide-induced acute kidney inflammation by modulating lysosomal stress. J. Res. Pharm. 2025;27(2):722-3.

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