title: Antioxidant activity of pomegranate juice reduces emphysematous changes and injury secondary to cigarette smoke in an animal model and human alveolar cells.
abstract: BACKGROUND
  Cigarette smoke (CS) increases oxidative stress (OS) in the lungs. Pomegranate juice (PJ) possesses potent antioxidant activities, attributed to its polyphenols. This study investigates the effects of PJ on the damaging effects of CS in an animal model and on cultured human alveolar cells (A549).
  
  
  METHODS
  Male C57BL/6J mice were divided into the following groups: Control, CS, CS + PJ, and PJ. Acute CS exposure was for 3 days, while chronic exposure was for 1 and 3 months (5 days of exposure/week). PJ groups received daily 80 μmol/kg via bottle, while other groups received distilled water. At the end of the experiments, different parameters were studied: 1) expression levels of inflammatory markers, 2) apoptosis, 3) OS, and 4) histopathological changes. In vitro, A549 cells were pretreated for 48 hours with either PJ (0.5 μM) or vehicle. Cells were then exposed to increasing concentrations of CS extracted from collected filters. Cell viability was assessed by counting of live and dead cells with trypan blue staining.
  
  
  RESULTS
  Acutely, a significant increase in interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α expression, apoptosis, and OS was noted in CS when compared to Control. PJ significantly attenuated the expression of inflammatory mediators, apoptosis, and OS. Chronically (at 1 and 3 months), increased expression of TNF-α was observed, and lung sections demonstrated emphysematous changes when compared to Control. PJ supplementation to CS animals attenuated the increased expression of TNF-α and normalized lung cytoarchitecture. At the cellular level, CS extract reduced cellular proliferation and triggered cellular death. Pretreatment with PJ attenuated the damaging effects of CS extract on cultured human alveolar cells.
  
  
  CONCLUSIONS
  The expression of inflammatory mediators associated with CS exposure and the emphysematous changes noted with chronic CS exposure were reduced with PJ supplementation. In vitro, PJ attenuated the damaging effects of CS extract on cultured human alveolar cells.
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, American University of Beirut, Beirut, Lebanon.
authors.forename: Ahmad
authors.initials: A
authors.lastname: Husari
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, American University of Beirut, Beirut, Lebanon.
authors.forename: Yasmine
authors.initials: Y
authors.lastname: Hashem
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, American University of Beirut, Beirut, Lebanon.
authors.forename: Hala
authors.initials: H
authors.lastname: Bitar
authors.affiliation: Department of Pediatrics and Adolescent Medicine, Division of Pediatric Infectious Diseases, American University of Beirut, Beirut, Lebanon; Department of Biochemistry and Molecular Genetics, American University of Beirut, Beirut, Lebanon.
authors.forename: Ghassan
authors.initials: G
authors.lastname: Dbaibo
authors.affiliation: Department of Pathology and Laboratory Medicine, American University of Beirut, Beirut, Lebanon.
authors.forename: Ghazi
authors.initials: G
authors.lastname: Zaatari
authors.affiliation: Department of Anatomy, Cell Biology and Physiological Sciences, Faculty of Medicine, American University of Beirut, Beirut, Lebanon.
authors.forename: Marwan
authors.initials: M
authors.lastname: El Sabban
mesh_terms: D056809:Alveolar Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002478:Cells, Cultured; D004195:Disease Models, Animal; D000067030:Fruit and Vegetable Juices; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D029561:Lythraceae; D051379:Mice; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress / Q000187:drug effects; D059808:Polyphenols / Q000494:pharmacology*; D011656:Pulmonary Emphysema / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D017382:Reactive Oxygen Species / Q000378:metabolism; D012907:Smoking / Q000009:adverse effects / Q000378:metabolism / Q000503:physiopathology; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000975:Antioxidants; D053583:Interleukin-1beta; D015850:Interleukin-6; D059808:Polyphenols; D017382:Reactive Oxygen Species; D014028:Tobacco Smoke Pollution; D014409:Tumor Necrosis Factor-alpha
keywords: acute lung injury; antioxidants; cigarette smoke; emphysema; inflammatory mediators; pomegranate extract; reactive oxygen species