title: Curcumin inhibits paraquat induced lung inflammation and fibrosis by extracellular matrix modifications in mouse model.
abstract: OBJECTIVE
  Paraquat (PQ), a potent herbicide can cause severe toxicity. We report here that fibroproliferation phase of acute lung injury (ALI) is initiated much earlier (within 48 h) after PQ intoxication than previously reported (after 2 weeks) and we aimed to study the protective effects of intranasal curcumin as new therapeutic strategy in mouse model.
  
  
  METHODS
  Mice (Park's strain) were divided into five experimental groups (I) control, received only saline (0.9 % NaCl) (II) PQ, mice intoxicated with PQ (50 mg/kg, i.p., single dose); (III) curcumin, treated with curcumin (5 mg/kg, i.n) an hour before PQ administration; (IV)Veh, DMSO (equal volume to curcumin) given an hour before PQ exposure; (V) DEXA, mice treated with dexamethasone (1 mg/kg, i.p) before an hour of PQ intoxication. After 48 h of the PQ exposure, all mice were sacrificed and samples were analyzed.
  
  
  RESULTS
  Pretreatment with intranasal curcumin (5 mg/kg) could modify the PQ-intoxication (50 mg/kg, i.p) induced structural remodeling of lung parenchyma at an early phase of acute lung injury. Significant increase in inflammatory cell count, reactive oxygen species and hydroxyproline levels were decreased after curcumin pretreatment (all p < 0.05). Histological examination and zymography results were also found consistent.
  
  
  CONCLUSIONS
  Our results show that curcumin pretreatment decreased the expression of alpha smooth muscle actin (α-SMA), matrix metalloproteinases-9 (MMP-9) and changed the expression of tissue inhibitors of metalloproteinase (TIMP-1) after PQ intoxication. Single toxic dose of PQ has initiated fibroproliferation within 48 h and intranasal curcumin may prove as new therapeutic strategy for PQ induced ALI and fibroproliferation.
authors.affiliation: Department of Zoology, MMV, Banaras Hindu University, Varanasi, 221005, India.
authors.forename: Namitosh
authors.initials: N
authors.lastname: Tyagi
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: D055371:Acute Lung Injury / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D000281:Administration, Intranasal; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D003094:Collagen / Q000378:metabolism; D003474:Curcumin / Q000008:administration & dosage / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005355:Fibrosis; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008297:Male; D008815:Mice, Inbred Strains; D018384:Oxidative Stress / Q000187:drug effects; D010269:Paraquat / Q000633:toxicity*; D011014:Pneumonia / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*
chemical_list: D000893:Anti-Inflammatory Agents; D003094:Collagen; D003474:Curcumin; D010269:Paraquat
keywords: Acute lung injury; Fibroproliferation and curcumin; Inflammation; Paraquat