title: Curcumin inhibits lipopolysaccharide (LPS)-induced endotoxemia and airway inflammation through modulation of sequential release of inflammatory mediators (TNF-α and TGF-β1) in murine model.
abstract: OBJECTIVE
  Curcumin (diferuloylmethane), a major component of turmeric is well known for its anti-inflammatory potential. Present study investigates sequential release of inflammatory mediators post LPS challenge (10 mg/kg,i.p.) causing lung inflammation and its modulation by curcumin through different routes (20 mg/kg, i.p and 10 mg/kg, i.n.) in murine model. Dexamethasone (1 mg/kg, i.p) was used as standard drug.
  
  
  METHODS
  Lung Inflammation was evaluated by histopathological analysis, myeloperoxidase (MPO) activity followed by inflammatory cell count and total protein content measurements in bronchoalveolar fluid (BALF). Reactive oxygen species (ROS), nitrite and TNF-α levels were measured as markers of endotoxin shock at different time points (1-72 h). The mRNA expression of transforming growth factors-β1 (TGF-β1), iNOS and Toll-like receptor-4 (TLR-4) were measured followed by Masson's trichrome staining and hydroxyproline levels as collagen deposition marker leading to fibrotic changes in lungs.
  
  
  RESULTS
  We found that LPS-induced lung inflammation and injury was maximum 24-h post LPS challenge shown by MPO and histological analysis which was further supported by elevated nitrite and ROS levels whereas TNF-α level was highest after 1 h. Endotoxin-induced mortality was significantly reduced in curcumin (i.p) pretreatment groups up to 72-h post LPS challenge. Significant inhibition in mRNA expression of iNOS, TGF-β1 and TNF-α level was noted after curcumin treatment along with lowered MPO activity, inflammatory cell count, ROS, nitrite levels and collagen deposition in lungs.
  
  
  CONCLUSIONS
  Our results suggest that higher endotoxin dose causes inflammatory mediator release in chronological order which tend to increase with time and reached maximum after 24-h post-endotoxin (LPS) exposure. Intraperitoneal route of curcumin administration was better in modulating inflammatory mediator release in early phase as compared to intranasal route of administration. It can be used as supplementary therapeutic intervention at early stage of endotoxemia, having fewer side effects.
authors.affiliation: Department of Zoology, MMV, Banaras Hindu University, Varanasi, 221005, India.
authors.forename: Asha
authors.initials: A
authors.lastname: Kumari
authors.affiliation: Department of Biochemistry, Institute of Medical Sciences, Banaras Hindu University, Varanasi, 221005, India.
authors.forename: D
authors.initials: D
authors.lastname: Dash
authors.affiliation: Department of Zoology, MMV, Banaras Hindu University, Varanasi, 221005, India. rashmirs98@rediffmail.com.
authors.forename: Rashmi
authors.initials: R
authors.lastname: Singh
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D003474:Curcumin / Q000494:pharmacology*; D004195:Disease Models, Animal; D019446:Endotoxemia / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D011014:Pneumonia / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D051197:Toll-Like Receptor 4; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D009195:Peroxidase; D052247:Nitric Oxide Synthase Type II; D003474:Curcumin
keywords: Endotoxemia; Fibrosis; Inflammation; Mortality