title: Involvement of the Bufadienolides in the Detection and Therapy of the Acute Respiratory Distress Syndrome.
abstract: The acute respiratory distress syndrome (ARDS) represents a major challenge for clinicians as well as basic scientists. The mortality rate for ARDS has been maintained within the range of 40-52%. The authors have examined the involvement of the "cardiotonic steroids" in the pathogenesis and therapy of ARDS. We have studied the possible role of the bufadienolide, marinobufagenin (MBG), in the pathogenesis of ARDS in both a rat model of ARDS and in patients afflicted with that disorder. In addition, the potential therapeutic benefit of an antagonist of MBG, resibufogenin (RBG), in an animal model has been evaluated.
  
  
  
  A syndrome resembling human ARDS was produced in the rat by exposing the animals to 100% oxygen for 48 h. In other animals, RBG was administered to these "hyperoxic" rats, and the serum MBG was measured. In human ICU patients, urinary samples were examined for levels of MBG, and the values were compared to those obtained from other ICU patients admitted with diagnoses other than ARDS.
  
  
  
  (1) Exposure of rats to hyperoxia produced a histologic picture which resembled that of human ARDS. (2) Serum levels of MBG in the "hyperoxic" rats substantially exceeded those obtained in animals exposed to ambient oxygen levels and were reduced to normal by RBG. (3) In ARDS patients, substantial elevations in urinary MBG were obtained compared to those in non-ARDS ICU patients.
  
  
  
  MBG may serve as an important biomarker for the development of ARDS, and RBG may represent a preventative/therapy in this disorder.
authors.affiliation: Department of Veterinary Pathobiology, School of Veterinary Medicine and Biosciences, Texas A&M University, VMS Room 216, 4467 TAMU, College Station, TX, 77843-4467, USA.
authors.forename: Mir M K
authors.initials: MMK
authors.lastname: Abbas
authors.affiliation: Pulmonary Disease Critical Care, Memorial Hermann Hospital, Houston, TX, USA.
authors.forename: B
authors.initials: B
authors.lastname: Patel
authors.affiliation: Department of Veterinary Pathobiology, School of Veterinary Medicine and Biosciences, Texas A&M University, VMS Room 216, 4467 TAMU, College Station, TX, 77843-4467, USA.
authors.forename: Q
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Division of Neonatal-Perinatal Medicine, Department of Pediatrics, Texas Children's Hospital, Baylor College of Medicine, 1102 Bates Ave. Suite C.530.04, Houston, TX, 77030, USA.
authors.forename: W
authors.initials: W
authors.lastname: Jiang
authors.affiliation: Division of Neonatal-Perinatal Medicine, Department of Pediatrics, Texas Children's Hospital, Baylor College of Medicine, 1102 Bates Ave. Suite C.530.04, Houston, TX, 77030, USA. bxmoorth@texaschildrenshospital.org.
authors.forename: B
authors.initials: B
authors.lastname: Moorthy
authors.affiliation: Department of Pathology, Houston Methodist Research Institute, Houston, TX, USA.
authors.forename: R
authors.initials: R
authors.lastname: Barrios
authors.affiliation: Department of Veterinary Pathobiology, School of Veterinary Medicine and Biosciences, Texas A&M University, VMS Room 216, 4467 TAMU, College Station, TX, 77843-4467, USA. jbpuschett@aol.com.|Department of Medicine, School of Medicine, Texas A&M University, College Station, TX, USA. jbpuschett@aol.com.
authors.forename: J B
authors.initials: JB
authors.lastname: Puschett
mesh_terms: D055371:Acute Lung Injury / Q000209:etiology / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control*; D000818:Animals; D015415:Biomarkers / Q000097:blood / Q000652:urine; D002018:Bufanolides / Q000008:administration & dosage* / Q000097:blood* / Q000652:urine*; D016022:Case-Control Studies; D004195:Disease Models, Animal; D006801:Humans; D018496:Hyperoxia / Q000150:complications; D011650:Pulmonary Alveoli / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D011654:Pulmonary Edema / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control; D051381:Rats; D012128:Respiratory Distress Syndrome / Q000209:etiology / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control*; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; D002018:Bufanolides; C005734:bufogenin; C093896:marinobufagenin
keywords: ARDS; Hyperoxia; Marinobufagenin; Resibufogenin