title: Thaliporphine derivative improves acute lung injury after traumatic brain injury.
abstract: Acute lung injury (ALI) occurs frequently in patients with severe traumatic brain injury (TBI) and is associated with a poor clinical outcome. Aquaporins (AQPs), particularly AQP1 and AQP4, maintain water balances between the epithelial and microvascular domains of the lung. Since pulmonary edema (PE) usually occurs in the TBI-induced ALI patients, we investigated the effects of a thaliporphine derivative, TM-1, on the expression of AQPs and histological outcomes in the lung following TBI in rats. TM-1 administered (10 mg/kg, intraperitoneal injection) at 3 or 4 h after TBI significantly reduced the elevated mRNA expression and protein levels of AQP1 and AQP4 and diminished the wet/dry weight ratio, which reflects PE, in the lung at 8 and 24 h after TBI. Postinjury TM-1 administration also improved histopathological changes at 8 and 24 h after TBI. PE was accompanied with tissue pathological changes because a positive correlation between the lung injury score and the wet/dry weight ratio in the same animal was observed. Postinjury administration of TM-1 improved ALI and reduced PE at 8 and 24 h following TBI. The pulmonary-protective effect of TM-1 may be attributed to, at least in part, downregulation of AQP1 and AQP4 expression after TBI.
authors.affiliation: Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 110, Taiwan ; Division of Orthodontics & Dentofacial Orthopedics and Pedodontics, Department of Dentistry, Tri-Service General Hospital, Taipei 114, Taiwan.
authors.forename: Gunng-Shinng
authors.initials: GS
authors.lastname: Chen
authors.affiliation: Division of Neurosurgery, Department of Surgery, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 23142, Taiwan ; School of Medicine, Tzu Chi University, Hualien 97004, Taiwan.
authors.forename: Kuo-Feng
authors.initials: KF
authors.lastname: Huang
authors.affiliation: Teaching Department of Medicine, China Medical University, Taichung 40402, Taiwan.
authors.forename: Chien-Chu
authors.initials: CC
authors.lastname: Huang
authors.affiliation: Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 110, Taiwan ; Department of Physiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan.
authors.forename: Jia-Yi
authors.initials: JY
authors.lastname: Wang
mesh_terms: D055371:Acute Lung Injury / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D000818:Animals; D001060:Aporphines / Q000008:administration & dosage*; D051398:Aquaporin 1 / Q000096:biosynthesis / Q000235:genetics; D051401:Aquaporin 4 / Q000096:biosynthesis / Q000235:genetics; D001930:Brain Injuries / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D051381:Rats
chemical_list: D001060:Aporphines; C496022:Aqp1 protein, rat; C496032:Aqp4 protein, rat; D051401:Aquaporin 4; D051398:Aquaporin 1; C080702:thaliporphine