The effect of quercetin, a flavonoid, on lung injury caused by sepsis

Quercetin and sepsis-related lung injury



sepsis, quercetin, acute respiratory distress syndrome, lung


Background/Aim: Lung injury is frequently observed in cases with sepsis, which can lead to conditions that progress to acute respiratory distress syndrome (ARDS) causing mortality. There is no specific treatment for sepsis or sepsis-induced lung injury. Antioxidant therapy has been one of the most prominent options for treatment, according to pathophysiological studies. The aim of this study was to investigate the effects of quercetin, a powerful antioxidant, on sepsis and sepsis-related lung injury.

Methods: Thirty-two adult male Sprague Dawley rats were divided into five groups. The control group (CNRL) received 1.5 ml saline via the intragastric route. The quercetin group (QUER [n=5]) underwent no sepsis procedure and received 20 mg/kg quercetin via the intragastric route starting 15 days before the procedure. The sham group (SHAM [n=6]) underwent a surgical incision and received 1.5 ml intragastric olive oil (quercetin dissolves in oil). The sepsis group (SEPS [n=7]) underwent the sepsis procedure. The sepsis and quercetin group (SEPS+QUER [n=7]) underwent the sepsis procedure and received 20 mg/kg quercetin via the intragastric route for 15 days before the procedure. Cecal ligation and puncture methods were used to induce sepsis. While ALT, AST, LDH, GGT and CRP values were analyzed from rat blood, MDA and GSH levels were analyzed from lung tissue.

Results: The results showed that quercetin reduced neutrophil infiltration (TLIS 3.5 [0.26] in the SEPS group vs TLIS 2.75 [0.29] in the SEPS+QUER group [P=0.01]), intra-alveolar macrophage count (SEPS vs SEPS+QUER [P=0.01]) and cell proliferation (SEPS vs SEPS+QUER [P=0.01]), and that it helped to preserve lung anatomy during sepsis. It was observed that MDA levels in the lung tissue decreased with the treatment of quercetin to septic rats (SEPS vs SEPS+QUER [P=0.046]).

Conclusion: These findings suggest that quercetin may be a potential treatment option for sepsis. However, more studies are needed to determine whether quercetin is a viable option as a therapeutic strategy in patients.


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Rhodes A, Evans LE, Alhazzani W, Levy MM, Antonelli M, Ferrer R, et al. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016. Intensive Care Med. 2017;43(3):304-77. doi: 10.1007/s00134-017-4683-6. DOI:

Zhang HB, Sun LC, Zhi LD, Wen QK, Qi ZW, Yan ST, et al. Astilbin alleviates sepsis-induced acute lung injury by inhibiting the expression of macrophage inhibitory factor in rats. Arch Pharm Res. 2017;40(10):1176-85. doi: 10.1007/s12272-016-0857-y. DOI:

Yeh CH, Yang JJ, Yang ML, Li YC, Kuan YH. Routine decreases lipopolysaccharide-induced acute lung injury via inhibition of oxidative stress and the MAPK-NF-κB pathway. Free Radic Biol Med. 2014;69:249-57. doi: 10.1016/j.freeradbiomed.2014.01.028. DOI:

Gerin F, Sener U, Erman H, Yilmaz A, Aydin B, Armutcu F, et al. The Effects of Quercetin on Acute Lung Injury and Biomarkers of Inflammation and Oxidative Stress in the Rat Model of Sepsis. Inflammation. 2016;39(2):700-5. doi: 10.1007/s10753-015-0296-9. DOI:

Huang R, Zhong T, Wu H. Quercetin protects against lipopolysaccharide-induced acute lung injury in rats through suppression of inflammation and oxidative stress. Arch Med Sci. 2015;11(2):427-32. doi: 10.5114/aoms.2015.50975. DOI:

Bahar E, Lee GH, Bhattarai KR, Lee HY, Kim HK, Handigund M, et al. Protective role of quercetin against manganese-induced injury in the liver, kidney, and lung; and hematological parameters in acute and subchronic rat models. Drug Des Devel Ther. 2017;5(11):2605-19. doi: 10.2147/DDDT.S143875. DOI:

Dogan Z, Cetin A, Elibol E, Vardi N, Turkoz Y. Effects of ciprofloxacin and quercetin on fetal brain development: a biochemical and histopathological study. J Matern Fetal Neonatal Med. 2019;32(11):1783-91. doi: 10.1080/14767058.2017.1418222. DOI:

Kılbaş, Z. 05.08.2022.

Mihara M, Uchiyama M. Determination of malonaldehyde precursor in tissues by thiobarbituric acid test. Anal Biochem. 1978;86(1):271-8. doi: 10.1016/0003-2697(78)90342-1. DOI:

Uraz S, Tahan V, Aygun C, Eren F, Unluguzel G, Yuksel M, et al. Role of ursodeoxycholic acid in prevention of methotrexate-induced liver toxicity. Dig Dis Sci. 2008;53(4):1071-7. doi: 10.1007/s10620-007-9949-3. DOI:

Mathew D, Nair CK, Jacob JA, Biswas N, Mukherjee T, Kapoor S, et al. Ascorbic acid monoglucoside as antioxidant and radioprotector. J Radiat Res. 2007;48(5):369-76. doi: 10.1269/jrr.07007. DOI:

Eşrefoğlu M, Gül M, Ateş B, Batçioğlu K, Selimoğlu MA. Antioxidative effect of melatonin, ascorbic acid and N-acetylcysteine on caerulein-induced pancreatitis and associated liver injury in rats. World J Gastroenterol. 2006;12(2):259-64. doi: 10.3748/wjg.v12.i2.259. DOI:

Kilciksiz S, Demirel C, Erdal N, Gürgül S, Tamer L, Ayaz L, et al. The effect of N-acetylcysteine on biomarkers for radiation-induced oxidative damage in a rat model. Acta Med Okayama. 2008;62(6):403-9. doi: 10.18926/AMO/30946.

Zhao H, Chen H, Xiaoyin M, Yang G, Hu Y, Xie K, et al. Autophagy Activation Improves Lung Injury and Inflammation in Sepsis. Inflammation. 2019;42(2):426-39. doi: 10.1007/s10753-018-00952-5. DOI:

Hu T, Shi JJ, Fang J, Wang Q, Chen YB, Zhang SJ. Quercetin ameliorates diabetic encephalopathy through SIRT1/ER stress pathway in db/db mice. Aging (Albany NY). 2020;12(8):7015-29. doi: 10.18632/aging.103059. DOI:

Karimi A, Naeini F, Asghari Azar V, Hasanzadeh M, Ostadrahimi A, Niazkar HR, et al. A comprehensive systematic review of the therapeutic effects and mechanisms of action of quercetin in sepsis. Phytomedicine. 2021;86:153567. doi: 10.1016/j.phymed.2021.153567. DOI:

Rittirsch D, Flierl MA, Ward PA. Harmful molecular mechanisms in sepsis. Nat Rev Immunol. 2008;8(10):776-87. doi: 10.1038/nri2402. DOI:

Abe R, Oda S, Sadahiro T, Nakamura M, Hirayama Y, Tateishi Y, et al. Gram-negative bacteremia induces greater magnitude of inflammatory response than Gram-positive bacteremia. Crit Care. 2010;14(2):R27. doi: 10.1186/cc8898. DOI:

Angus DC, Van Der Poll T. Severe sepsis and septic shock. NEJM. 2013;369(9):840-51. doi: 10.1056/NEJMra1208623. DOI:

Beutler B, Rietschel ET. Innate immune sensing and its roots: the story of endotoxin. Nat Rev Immunol. 2003 Feb;3(2):169-76. doi: 10.1038/nri1004. DOI:

Chen JC, Ho FM, Pei-Dawn Lee Chao, Chen CP, Jeng KC, Hsu HB, et al. Inhibition of iNOS gene expression by quercetin is mediated by the inhibition of IkappaB kinase, nuclear factor-kappa B and STAT1, and depends on heme oxygenase-1 induction in mouse BV-2 microglia. Eur J Pharmacol. 2005;521(1-3):9-20. doi: 10.1016/j.ejphar.2005.08.005. DOI:

Yilmaz MZ, Guzel A, Torun AC, Okuyucu A, Salis O, Karli R, et al. The therapeutic effects of anti-oxidant and anti-inflammatory drug quercetin on aspiration-induced lung injury in rats. J Mol Histol. 2014;45(2):195-203. doi: 10.1007/s10735-013-9542-3. DOI:

Sang A, Wang Y, Wang S, Wang Q, Wang X, Li X, et al. Quercetin attenuates sepsis-induced acute lung injury via suppressing oxidative stress-mediated ER stress through activation of SIRT1/AMPK pathways. Cell Signal. 2022;96:110363. doi: 10.1016/j.cellsig.2022.110363. DOI:

Wang XF, Song SD, Li YJ, Hu ZQ, Zhang ZW, Yan CG, et al. Protective Effect of Quercetin in LPS-Induced Murine Acute Lung Injury Mediated by cAMP-Epac Pathway. Inflammation. 2018;41(3):1093-103. doi: 10.1007/s10753-018-0761-3. DOI:

Liu N, Cao F, Li Q, Zhang Y, Zhang Z, Guan W. [Study of quercetin on pulmonary fibrosis by silica particles]. Wei Sheng Yan Jiu. 2014 Sep;43(5):814-8.

Zerin T, Kim YS, Hong SY, Song HY. Quercetin reduces oxidative damage induced by paraquat via modulating expression of antioxidant genes in A549 cells. J Appl Toxicol. 2013;33(12):1460-7. doi: 10.1002/jat.2812. DOI:

Chanjitwiriya K, Roytrakul S, Kunthalert D. Quercetin negatively regulates IL-1β production in Pseudomonas aeruginosa-infected human macrophages through the inhibition of MAPK/NLRP3 inflammasome pathways. PLoS One. 2020;15(8):e0237752. doi: 10.1371/journal.pone.0237752. DOI:

Alsharif KF, Almalki AA, Al-Amer O, Mufti AH, Theyab A, Lokman MS, et al. Oleuropein protects against lipopolysaccharide-induced sepsis and alleviates inflammatory responses in mice. IUBMB Life. 2020;72(10):2121-32. doi: 10.1002/iub.2347. DOI:

Zhao H, Liu Z, Liu W, Han X, Zhao M. Betulin attenuates lung and liver injuries in sepsis. Int Immunopharmacol. 2016;30:50-6. doi: 10.1016/j.intimp.2015.11.028. DOI:






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Bıçakcıoğlu M, Doğukan M, Duran M, Doğan Z, Aydın Türk B. The effect of quercetin, a flavonoid, on lung injury caused by sepsis: Quercetin and sepsis-related lung injury. J Surg Med [Internet]. 2023 Sep. 29 [cited 2024 Jul. 15];7(9):618-22. Available from: