Suberosin Alleviates Sepsis-Induced Lung Injury in A Rat Model of Cecal Ligation and Puncture.

BACKGROUND/AIMS Sepsis is one of the major problems encountered in intensive care units, causing organ damage and increasing mortality. Suberosin (SBR) is a type of coumarin with antioxidant and anti-inflammatory activities. The goal of this study is to explore the protective effects of SBR on the lungs in a rat model of sepsis. METHODS Male Wistar rats were utilized in this study. A cecal ligation and puncture (CLP) model was applied to induce sepsis. Rats were separated into six groups with nine animals in each group, including healthy control, SBR, CLP, and CLP + SBR (5, 10, and 20 mg/kg) groups. Superoxide dismutase (SOD), glutathione (GSH) enzyme activities, and malondialdehyde (MDA) level were measured via enzyme-linked immunosorbent assay (ELISA). The messenger RNA (mRNA) expressions of tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β) were evaluated by real-time polymerase chain reaction (RT-PCR). Histopathological changes in the lungs were investigated with hematoxylin and eosin (H&E). RESULTS MDA levels and GSH and SOD enzyme activities were negatively affected in the CLP group, but SBR treatment ameliorated these oxidative stress parameters in the SBR1-3 groups (p< 0.05). The mRNA expressions of TNF-α and IL-1β were increased in the CLP group, and SBR treatment decreased those expression levels in a dose-dependent manner (p < 0.05). Organ damage and necrosis were seen in the CLP group and were alleviated in the SBR3 group. Immunohistochemical (IHC) analysis of lung tissues demonstrated decreased TNF-α and IL-1β immunopositivity in the SBR1-3 groups (p< 0.05). CONCLUSIONS SBR ameliorated sepsis-related lung injury in a dose-dependent manner. This compound has significant potential as a future agent in the treatment of sepsis.

[1]  E. Akpinar,et al.  Protective Effects of Idebenone against Sepsis Induced Acute Lung Damage , 2021, Journal of investigative surgery : the official journal of the Academy of Surgical Research.

[2]  S. Karabulut,et al.  Effects of umbelliferone isolated from the Ferulago pauciradiata Boiss. & Heldr. Plant on cecal ligation and puncture-induced sepsis model in rats. , 2020, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[3]  Xiaogen Tao,et al.  Protective effects of melatonin on sepsis-induced liver injury and dysregulation of gluconeogenesis in rats through activating SIRT1/STAT3 pathway. , 2019, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[4]  I. Cinar,et al.  Ameliorative effect of gossypin against acute lung injury in experimental sepsis model of rats , 2019, Life sciences.

[5]  O. Sytar,et al.  Antioxidant and anticholinesterase potential of Ferulago cassia with farther bio-guided isolation of active coumarin constituents , 2019, South African Journal of Botany.

[6]  A. Hadjiakhoondi,et al.  Bioactive coumarins from the roots and fruits of Ferulago trifida Boiss., an endemic species to Iran , 2018, Natural product research.

[7]  Zhongxiang Xiao,et al.  Osthole Protects against Acute Lung Injury by Suppressing NF-κB-Dependent Inflammation , 2018, Mediators of inflammation.

[8]  Daniel J Patrick,et al.  Use of Severity Grades to Characterize Histopathologic Changes , 2018, Toxicologic pathology.

[9]  E. Zakynthinos,et al.  Role of Oxidative Stress and Mitochondrial Dysfunction in Sepsis and Potential Therapies , 2017, Oxidative medicine and cellular longevity.

[10]  Yeong Shik Kim,et al.  Pharmacological mechanism underlying anti-inflammatory properties of two structurally divergent coumarins through the inhibition of pro-inflammatory enzymes and cytokines , 2015, Journal of Inflammation.

[11]  Min Gao,et al.  Protective effect of astaxanthin against multiple organ injury in a rat model of sepsis. , 2015, The Journal of surgical research.

[12]  S. Han,et al.  Ursolic acid isolated from guava leaves inhibits inflammatory mediators and reactive oxygen species in LPS-stimulated macrophages , 2015, Immunopharmacology and immunotoxicology.

[13]  M. Abdollahi,et al.  Anticoagulant activity of isolated coumarins (suberosin and suberenol) and toxicity evaluation of Ferulago carduchorum in rats , 2014, Pharmaceutical biology.

[14]  Jianbo Sun,et al.  1,8-Cineol Attenuates LPS-Induced Acute Pulmonary Inflammation in Mice , 2014, Inflammation.

[15]  Y. Hseu,et al.  Toona sinensis Inhibits LPS-Induced Inflammation and Migration in Vascular Smooth Muscle Cells via Suppression of Reactive Oxygen Species and NF-κB Signaling Pathway , 2014, Oxidative medicine and cellular longevity.

[16]  Arthur S Slutsky,et al.  Acute Respiratory Distress Syndrome The Berlin Definition , 2012 .

[17]  P. Pelosi,et al.  Early and late effects of bone marrow-derived mononuclear cell therapy on lung and distal organs in experimental sepsis , 2011, Respiratory Physiology & Neurobiology.

[18]  C. Bondor,et al.  Multiplex cytokine profiling in patients with sepsis , 2011, APMIS : acta pathologica, microbiologica, et immunologica Scandinavica.

[19]  A. Basile,et al.  Antimicrobial and Antioxidant Activities of Coumarins from the Roots of Ferulago campestris (Apiaceae) , 2009, Molecules.

[20]  Jesús Blanco,et al.  Incidence, organ dysfunction and mortality in severe sepsis: a Spanish multicentre study , 2008, Critical care.

[21]  M. Wu,et al.  Suberosin inhibits proliferation of human peripheral blood mononuclear cells through the modulation of the transcription factors NF‐AT and NF‐κB , 2007, British journal of pharmacology.

[22]  Kirby I Bland,et al.  CECAL LIGATION AND PUNCTURE , 2005, Shock.

[23]  D. Hadjipavlou-Litina,et al.  Natural and synthetic coumarin derivatives with anti-inflammatory/ antioxidant activities. , 2004, Current pharmaceutical design.

[24]  Jonathan Cohen The immunopathogenesis of sepsis , 2002, Nature.

[25]  Y. Asakawa,et al.  Ferulagone: A New Monoterpene Ester from Ferulago thirkeana Essential Oil , 2002, Planta medica.

[26]  Thomas D. Schmittgen,et al.  Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. , 2001, Methods.

[27]  M. Gazouli,et al.  Chemical analysis and antimicrobial studies on three species of Ferulago from Greece. , 2000, Planta medica.

[28]  M. Arditi,et al.  Bacterial Lipopolysaccharide Activates NF-κB through Toll-like Receptor 4 (TLR-4) in Cultured Human Dermal Endothelial Cells , 2000, The Journal of Biological Chemistry.

[29]  J. Mitchell,et al.  Redox imbalance in the critically ill. , 1999, British medical bulletin.