title: Betulinic acid negates oxidative lung injury in surgical sepsis model.
abstract: BACKGROUND
  Sepsis commonly progresses to acute lung injury and is associated with high morbidity and mortality. Septic acute lung injury is characterized by severe oxidative stress response, remained refractory to present therapies, and new therapies need to be developed to improve further clinical outcomes. We determined the effect of betulinic acid (BA) on oxidative lung injury in mice using cecal ligation and puncture (CLP) model.
  
  
  METHODS
  Five groups of mice (six in each group) received three pretreatments at 24-h interval before surgery. Surgery was done 1 h after last dosing. Sham and CLP control group mice received vehicle. BA was administered to other three groups of mice at 3, 10, and 30 mg/kg dose. Lung and plasma samples were collected for analysis by sacrificing the mice at 18 h of surgery.
  
  
  RESULTS
  Compared with sham, CLP significantly increased total protein, nitrite, malondialdehyde, isoprostane, superoxide, protein carbonyl, oxidative stress index, inducible nitric oxide synthase protein, and histopathologic changes and reduced the superoxide dismutase, catalase activity, and total thiol levels in lungs and plasma, which were restored by BA pretreatment.
  
  
  CONCLUSIONS
  BA pretreatment decreased the levels of oxidants, increased the levels of antioxidants in lungs and plasma thereby reducing the oxidative lung injury in CLP mice. Additionally, BA was found to scavenge the superoxide and nitric oxide radical in vitro. Thus, BA is suggested to be effective in treatment of oxidative lung injury in sepsis.
authors.affiliation: Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Bareilly, Uttar Pradesh, India.
authors.forename: Madhu C
authors.initials: MC
authors.lastname: Lingaraju
authors.affiliation: Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Bareilly, Uttar Pradesh, India.
authors.forename: Nitya N
authors.initials: NN
authors.lastname: Pathak
authors.affiliation: Division of Bacteriology and Mycology, Indian Veterinary Research Institute, Bareilly, Uttar Pradesh, India.
authors.forename: Jubeda
authors.initials: J
authors.lastname: Begum
authors.affiliation: Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Bareilly, Uttar Pradesh, India.
authors.forename: Venkanna
authors.initials: V
authors.lastname: Balaganur
authors.affiliation: Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Bareilly, Uttar Pradesh, India.
authors.forename: Rafia A
authors.initials: RA
authors.lastname: Bhat
authors.affiliation: Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Bareilly, Uttar Pradesh, India.
authors.forename: Mahendra
authors.initials: M
authors.lastname: Ram
authors.affiliation: Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Bareilly, Uttar Pradesh, India.
authors.forename: Dhirendra
authors.initials: D
authors.lastname: Kumar
authors.affiliation: Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Bareilly, Uttar Pradesh, India.
authors.forename: Dinesh
authors.initials: D
authors.lastname: Kumar
authors.affiliation: Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Bareilly, Uttar Pradesh, India. Electronic address: sktandan@gmail.com.
authors.forename: Surendra K
authors.initials: SK
authors.lastname: Tandan
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use*; D000975:Antioxidants / Q000378:metabolism; D015237:Dinoprost / Q000031:analogs & derivatives / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D055370:Lung Injury / Q000209:etiology / Q000517:prevention & control*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D053978:Pentacyclic Triterpenes; D050050:Protein Carbonylation / Q000187:drug effects; D018805:Sepsis / Q000150:complications*; D013481:Superoxides / Q000378:metabolism; D014315:Triterpenes / Q000494:pharmacology / Q000627:therapeutic use*; D000094062:Betulinic Acid
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D009573:Nitrites; D053978:Pentacyclic Triterpenes; D014315:Triterpenes; D013481:Superoxides; C075750:8-epi-prostaglandin F2alpha; D009569:Nitric Oxide; D008315:Malondialdehyde; D015237:Dinoprost; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D000094062:Betulinic Acid
keywords: Antioxidants; Cecal ligation and puncture; Lung oxidative stress; Mice; Triterpenoid; iNOS