AccScience Publishing / GTM / Online First / DOI: 10.36922/gtm.2568
Submit to GTM
Cite this article
57
Download
986
Views
Journal Browser
Volume | Year
Issue
Search
Forthcoming Issue
Current Issue
View All
News and Announcements
View All
ORIGINAL RESEARCH ARTICLE

Hesperetin alleviates pulmonary injury in a blunt chest trauma-induced pulmonary contusion model in rats

Serkan Kaya1 ,  İhsan Karaboğa2* ,  Yasin Duran3 ,  Elif Polat4
Show Less
1 Department of Thoracic Surgery, Tekirdağ Dr. İsmail Fehmi Cumalioğlu State Hospital, Tekirdag, Türkiye
2 Department of Histology and Embryology, Kırklareli University, Faculty of Medicine, Kırklareli, Türkiye
3 Department of Pathology Laboratory Techniques, Vocational School of Health Services, Istanbul Rumeli University, Istanbul, Türkiye
4 Department of Histology and Embryology, Faculty of Medicine, Tekirdag Namık Kemal University, Tekirdag, Türkiye
5 Department of General Surgery, Faculty of Medicine, Tekirdag Namık Kemal University, Tekirdag, Türkiye
Global Translational Medicine 2024, 3(2), 2568 https://doi.org/10.36922/gtm.2568
Submitted: 29 December 2023 | Accepted: 14 May 2024 | Published: 11 June 2024
© 2024 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
Download PDF
Cite
XML
Abstract

Pulmonary contusion (PC), a condition that occurs frequently in severe thoracic injuries, is a significant contributor to mortality in those under the age of 40. Hesperetin, a natural flavonoid derivative of hesperidin, is a substance found in various citrus fruits such as oranges and grapefruits and possesses a variety of biological activities, including antiapoptotic, antioxidant, and anticancer effects. In the current study, we investigated the effect of hesperetin on pulmonary tissue structure, expression of some pro-inflammatory cytokines, and mediators in a PC model induced by blunt chest trauma. In this study, 18 adult male Wistar albino rats (8 – 10 weeks, 250 – 300 g) were used. The rats were divided into three groups: control, PC, and PC + hesperetin. Hesperetin administration (100 mg/kg/day oral) was completed for 7 days following induction of the model. The wet/dry weight ratio of pulmonary tissue was determined. Tumor necrosis factor alpha (TNFα) and malondialdehyde (MDA) in lung tissues, serum interleukin (IL)-6, and IL-1β levels were determined using the enzyme-linked immunosorbent assays. Pulmonary tissue specimens were examined histologically using hematoxylin-eosin and Masson trichrome staining. Inducible nitric oxide synthase (iNOS) activity was determined using immunohistochemical methods. Hesperetin administration reduced TNFα and iNOS activity, serum IL-1β, IL-6, MDA, and wet/dry weight ratio in pulmonary tissue to improve pulmonary function. Our results showed that administration of hesperetin prevents activation of local inflammatory mediators, thereby obstructing the proinflammatory cytokine cascade and tissue injury.

Keywords
Trauma
Tumor necrosis factor alpha
Malondialdehyde
Interleukin 6
Funding
None.
Conflict of interest
The authors declare that they have no competing interests.
References
  1. Ozdinc S, Oz G, Ozdemir C, et al. Melatonin: Is it an effective antioxidant for pulmonary contusion? J Surg Res. 2016;204(2):445-451. doi: 10.1016/j.jss.2016.05.020

 

  1. Bakan V, Kurutaş EB, Çıralık H, Gül M, Çelik A. Endogenous erythropoietin level and effects of exogenous erythropoietin in a rat model of blunt chest trauma-induced pulmonary contusion. Ulus Travma Acil Cerrahi Derg. 2016;22:322-327. doi: 10.5505/tjtes.2015.09483

 

  1. Dogrul BN, Kiliccalan I, Asci ES, Peker SC. Blunt trauma related chest wall and pulmonary injuries: An overview. Chin J Traumatol. 2020;23(3):125-138. doi: 10.1016/j.cjtee.2020.04.003

 

  1. Keskin Y, Bedel C, Beceren NG. Investigation of histopathological and radiological effects of surfactant treatment in an experimental female rat model of lung contusion. Iran J Basic Med Sci. 2019;22(10):1153-1157. doi: 10.22038/ijbms.2019.32357.8258

 

  1. Batchinsky AI, Weiss WB, Jordan BS, et al. Ventilation-perfusion relationships following experimental pulmonary contusion. J Appl Physiol (1985). 2007;103(3):895-902. doi: 10.1152/japplphysiol.00563.2006

 

  1. Türüt H, Ciralik H, Kilinc M, Ozbag D, Imrek SS. Effects of early administration of dexamethasone, N-acetylcysteine and aprotinin on inflammatory and oxidant-antioxidant status after lung contusion in rats. Injury. 2009;40(5): 521-527. doi: 10.1016/j.injury.2008.05.001

 

  1. Karaboğa I. Caffeic acid phenethyl ester ameliorates pulmonary inflammation and apoptosis reducing Nf-κβ activation in blunt pulmonary contusion model. Ulus Travma Acil Cerrahi Derg. 2019;25(5):433-439. doi: 10.5505/tjtes.2018.51694

 

  1. Wu X, Song X, Li N, Zhan L, Meng Q, Xia Z. Protective effects of dexmedetomidine on blunt chest trauma-induced pulmonary contusion in rats. J Trauma Acute Care Surg. 2013;74(2):524-530. doi: 10.1097/TA.0b013e31827d5de3

 

  1. Wu XJ, Xia ZY, Wang LL, et al. Effects of penehyclidine hydrochloride on pulmonary contusion from blunt chest trauma in rats. Injury. 2012;43(2):232-236. doi: 10.1016/j.injury.2011.10.009

 

  1. Chen Y, Tong H, Zhang W, et al. Curative effect of Xuebijing injection on severe pulmonary contusion. J Tradit Chin Med. 2013;33(6):743-751. doi: 10.1016/s0254-6272(14)60006-6

 

  1. Aksu B, Ayvaz S, Aksu F, et al. Effects of sphingosylphosphorylcholine against oxidative stress and acute lung ınjury ınduced by pulmonary contusion in rats. J Pediatr Surg. 2015;50:591-597. doi: 10.1016/j.jpedsurg.2014.06.007

 

  1. Samie A, Sedaghat R, Baluchnejadmojarad T, Roghani M. Hesperetin, a citrus flavonoid, attenuates testicular damage in diabetic rats via inhibition of oxidative stress, inflammation, and apoptosis. Life Sci. 2018;210:132-139. doi: 10.1016/j.lfs.2018.08.074

 

  1. Ramteke P, Yadav UCS. Hesperetin, a citrus bioflavonoid, prevents IL-1β-induced inflammation and cell proliferation in lung epithelial A549 cells. Indian J Exp Biol. 2019;57:7-14.

 

  1. Wang N, Geng C, Sun H, Wang X, Li F, Liu X. Hesperetin ameliorates lipopolysaccharide-induced acute lung injury in mice through regulating the TLR4-MyD88-NF-κB signaling pathway. Arch Pharm Res. 2019;42(12):1063-1070. doi: 10.1007/s12272-019-01200-6

 

  1. Ye J, Guan M, Lu Y, et al. Protective effects of hesperetin on lipopolysaccharide-induced acute lung injury by targeting MD2. Eur J Pharmacol. 2019;852:151-158. doi: 10.1016/j.ejphar.2019.02.042

 

  1. Raghavendran K, Davidson BA, Helinski JD, et al. A rat model for isolated bilateral lung contusion from blunt chest trauma. Anesth Analg. 2005;101(5):1482-1489. doi: 10.1213/01.ANE.0000180201.25746.1F

 

  1. Kao MC, Jan WC, Tsai PS, Wang TY, Huang CJ. Magnesium sulfate mitigates lung injury induced by bilateral lower limb ischemia-reperfusion in rats. J Surg Res. 2011;171(1): e97-e106. doi: 10.1016/j.jss.2011.03.028

 

  1. Chen F, Liu Z, Wu W, et al. An essential role for TH 2-type responses in limiting acute tissue damage during experimental helminth infection. Nat Med. 2012;18(2): 260-266. doi: 10.1038/nm.2628

 

  1. Choi D, Kim CL, Kim JE, Mo JS, Jeong HS. Hesperetin inhibit EMT in TGF-β treated podocyte by regulation of mTOR pathway. Biochem Biophys Res Commun. 2020;528:154-159. doi: 10.1016/j.bbrc.2020.05.087

 

  1. Aboismaiel MG, El-Mesery M, El-Karef A, El-Shishtawya MM. Hesperetin upregulates Fas/FasL expression and potentiates the antitumor effect of 5-fluorouracil in rat model of hepatocellular carcinoma. Egypt J Basic Appl Sci. 2020;7:20-34. doi: 10.1080/2314808X.2019.1707627

 

  1. Lin Z, Fu C, Yan Z, et al. The protective effect of hesperetin in osteoarthritis: An in vitro and in vivo study. Food Funct. 2020;11(3):2654-2666. doi: 10.1039/c9fo02552a

 

  1. Yunita E, Muflikhasari HA, Ilmawati GPN, Meiyanto E, Hermawan A. Hesperetin alleviates doxorubicin-induced migration in 4T1 breast cancer cells. Future J Pharm Sci. 2020;6(1):23. doi: 10.1186/s43094-020-00036-y

 

  1. Zhang J, Lei H, Hu X, Dong W. Hesperetin ameliorates DSS-induced colitis by maintaining the epithelial barrier via blocking RIPK3/MLKL necroptosis signaling. Eur J Pharmacol. 2020;873:172992. doi: 10.1016/j.ejphar.2020.172992

 

  1. Bıçakçı N, Karaboğa I, Dökmeci AH, Güzel S, Fidanol Erboğa Z. Cardioprotective effect of caffeic acid phenethyl ester on cardiac contusion following blunt chest trauma in rats. Biotech Histochem. 2019;94(6):442-448. doi: 10.1080/10520295.2019.1586999

 

  1. Broderick SR. Hemothorax: Etiology, diagnosis, and management. Thorac Surg Clin. 2013;23:89-96, vi-vii. doi: 10.1016/j.thorsurg.2012.10.003

 

  1. Karaboğa I. Caffeic acid phenethyl ester (CAPE) suppresses systemic inflammation in rat trauma model. J Apither. 2018;3(2):31-35. doi: 10.5455/ja.20180702102008

 

  1. Relja B, Yang B, Bundkirchen K, Xu B, Köhler K, Neunaber C. Different experimental multiple trauma models induce comparable inflammation and organ injury. Sci Rep. 2020;10(1):20185. doi: 10.1038/s41598-020-76499-z

 

  1. Armutcu F, Akyol S, Ustunsoy S, Turan FF. Therapeutic potential of caffeic acid phenethyl ester and its anti-inflammatory and immunomodulatory effects (Review). Exp Ther Med. 2015;9:1582-1588. doi: 10.3892/etm.2015.2346

 

  1. Lai WY, Wang JW, Huang BT, Lin EP, Yang PC. A novel TNF-α-targeting aptamer for TNF-α-mediated acute lung injury and acute liver failure. Theranostics. 2019;9(6): 1741-1751. doi: 10.7150/thno.30972

 

  1. Böhm F, Köhler UA, Speicher T, Werner S. Regulation of liver regeneration by growth factors and cytokines. EMBO Mol Med. 2010;2(8):294-305. doi: 10.1002/emmm.201000085

 

  1. Meng QT, Xia ZY, Luo T, et al. Ligustrazine attenuates acute lung injury induced by blunt chest trauma. Saudi Med J. 2012;33(2):139-145.

 

  1. Ateş G, Yaman F, Bakar B, Kısa Ü, Atasoy P, Büyükkoçak Ü. Evaluation of the systemic antiinflammatory effects of levosimendan in an experimental blunt thoracic trauma model. Ulus Travma Acil Cerrahi Derg. 2017;23:368-376. doi: 10.5505/tjtes.2016.26786

 

  1. Ricciardolo FLM, Sterk PJ, Gaston B, Folkerts G. Nitric oxide in health and disease of the respiratory system. Physiol Rev. 2004;84(3):731-765. doi: 10.1152/physrev.00034.2003

 

  1. Sahin H, Yener AU, Karaboga I, et al. Protective effect of gel form of gastric gavage applicated Aloe vera on ischemia reperfusion injury in renal and lung tissue. Cell Mol Biol (Noisy-le-grand). 2017;63:34-39. doi: 10.14715/cmb/2017.63.12.9

 

  1. El‐Awady MS, Said E, Baraka HN. Acylated catalpol diglycoside ameliorates lipopolysaccharides‐induced acute lung injury through inhibition of iNOS and TNF‐α expression. J Biochem Mol Toxicol. 2018;32:e22214. doi: 10.1002/jbt.22214

 

  1. Rungsung S, Singh TU, Rabha DJ, et al. Luteolin attenuates acute lung injury in experimental mouse model of sepsis. Cytokine. 2018;110:333-343. doi: 10.1016/j.cyto.2018.03.042

 

  1. Basaran UN, Ayvaz S, Aksu B, et al. Desferrioxamine reduces oxidative stress in the lung contusion. ScientificWorldJournal. 2013;2013:376959. doi: 10.1155/2013/376959

 

  1. Dolkart O, Amar E, Shapira S, Marmor S, Steinberg EL, Weinbroum AA. Protective effects of rosuvastatin in a rat model of lung contusion: Stimulation of the cyclooxygenase 2-prostaglandin E-2 pathway. Surgery. 2015;157(5):944-953. doi: 10.1007/s10753-016-0409-0

 

  1. Kozan A, Kilic N, Alacam H, Guzel A, Guvenc T, Acikgoz M. The effects of dexamethasone and L-Name on acute lung injury in rats with lung contusion. Inflammation. 2016;39(5):1747-1756.

 

  1. Akgül AG, Şahin D, Temel U, et al. Effect of nitric oxide synthase inhibitors in acute lung injury due to blunt lung trauma in rats. Turk Gogus Kalp Damar Cerrahisi Derg. 2019;27:63-72. doi: 10.5606/tgkdc.dergisi.2019.15936

 

  1. Kim JY, Jung KJ, Choi JS, Chung HY. Modulation of the age‐related nuclear factor‐kappaB (NF‐kappaB) pathway by hesperetin. Aging Cell. 2006;5(5):401-411. doi: 10.1111/j.1474-9726.2006.00233.x

 

  1. Bai X, Yang P, Zhou Q, et al. The protective effect of the natural compound hesperetin against fulminant hepatitis in vivo and in vitro. Br J Pharmacol. 2017;174:41-56. doi: 10.1111/bph.13645

 

  1. Polat FR, Karaboga I, Polat MS, Erboga Z, Yilmaz A, Güzel S. Effect of hesperetin on inflammatory and oxidative status in trinitrobenzene sulfonic acid-induced experimental colitis model. Cell Mol Biol (Noisy-le-grand). 2018;64(11):58-65. doi: 10.14715/cmb/2018.64.11.11

 

  1. Jo SH, Kim ME, Cho JH, et al. Hesperetin inhibits neuroinflammation on microglia by suppressing inflammatory cytokines and MAPK pathways. Arch Pharm Res. 2019;42:695-703. doi: 10.1007/s12272-019-01174-5

 

  1. Ayvaz S, Aksu B, Karaca T, et al. Effects of methylene blue in acute lung injury induced by blunt chest trauma. Hippokratia. 2014;18:50-56.

 

  1. Baker TA, Romero J, Bach HH 4th Strom JA, Gamelli RL, Majetschak M. Effects of exogenous ubiquitin in a polytrauma model with blunt chest trauma. Crit Care Med. 2012;40:2376-2384. doi: 10.1097/CCM.0b013e3182514ed9

 

  1. Wang J, Zhu H, Yang Z, Liu Z. Antioxidative effects of hesperetin against lead acetate-induced oxidative stress in rats. Indian J Pharmacol. 2013;45(4):395-398. doi: 10.4103/0253-7613.115015

 

  1. Topcu-Tarladacalisir Y, Tarladacalisir T, Sapmaz-Metin M, et al. N-Acetylcysteine counteracts oxidative stress and protects alveolar epithelial cells from lung contusion-induced apoptosis in rats with blunt chest trauma. J Mol Histol. 2014;45(4):463-471. doi: 10.1007/s10735-014-9563-6

 

  1. Trivedi PP, Kushwaha S, Tripathi DN, Jena GB. Cardioprotective effects of hesperetin against doxorubicin-induced oxidative stress and DNA damage in rat. Cardiovasc Toxicol. 2011;11(3):215-225. doi: 10.1007/s12012-011-9114-2
Share
Back to top
Global Translational Medicine, Electronic ISSN: 2811-0021 Print ISSN: 3060-8600, Published by AccScience Publishing
We use cookies on our website to ensure you get the best experience.
Read more about our cookies here
Accept