title: Adjuvant potential of selegiline in attenuating organ dysfunction in septic rats with peritonitis.
abstract: Selegiline, an anti-Parkinson drug, has antioxidant and anti-apoptotic effects. To explore the effect of selegiline on sepsis, we used a clinically relevant animal model of polymicrobial sepsis. Cecal ligation and puncture (CLP) or sham operation was performed in male rats under anesthesia. Three hours after surgery, animals were randomized to receive intravenously selegiline (3 mg/kg) or an equivalent volume of saline. The administration of CLP rats with selegiline (i) increased arterial blood pressure and vascular responsiveness to norepinephrine, (ii) reduced plasma liver and kidney dysfunction, (iii) attenuated metabolic acidosis, (iv) decreased neutrophil infiltration in liver and lung, and (v) improved survival rate (from 44% to 65%), compared to those in the CLP alone rats. The CLP-induced increases of plasma interleukin-6, organ superoxide levels, and liver inducible nitric oxide synthase and caspase-3 expressions were ameliorated by selegiline treatment. In addition, the histological changes in liver and lung were significantly attenuated in the selegiline -treated CLP group compared to those in the CLP group. The improvement of organ dysfunction and survival through reducing inflammation, oxidative stress and apoptosis in peritonitis-induced sepsis by selegiline has potential as an adjuvant agent for critical ill.
authors.affiliation: Department of Anesthesiology, Taipei Veterans General Hospital, and National Yang-Ming University, Taipei, Taiwan, R.O.C.; Department of Anesthesiology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, R.O.C.
authors.forename: Cheng-Ming
authors.initials: CM
authors.lastname: Tsao
authors.affiliation: Department of Pharmacology, National Defense Medical Center, Taipei, Taiwan, R.O.C.
authors.forename: Jhih-Gang
authors.initials: JG
authors.lastname: Jhang
authors.affiliation: Department of Nursing, Kang-Ning Junior College of Medical Care and Management, Taipei, Taiwan, R.O.C.; Department of Physiology, National Defense Medical Center, Taipei, Taiwan, R.O.C.
authors.forename: Shiu-Jen
authors.initials: SJ
authors.lastname: Chen
authors.affiliation: Graduate Institute of Aerospace and Undersea Medicine, National Defense Medical Center, Taipei, Taiwan, R.O.C.
authors.forename: Shuk-Man
authors.initials: SM
authors.lastname: Ka
authors.affiliation: Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, R.O.C.; Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan, R.O.C.
authors.forename: Tao-Cheng
authors.initials: TC
authors.lastname: Wu
authors.affiliation: Department of Anesthesiology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, R.O.C.; Department of Anesthesiology, Tungs' Taichung MetroHarbor Hospital, Taichung, Taiwan, R.O.C.
authors.forename: Wen-Jinn
authors.initials: WJ
authors.lastname: Liaw
authors.affiliation: Department of Anesthesiology, Cheng-Hsin General Hospital, Taipei, Taiwan, R.O.C.
authors.forename: Hsieh-Chou
authors.initials: HC
authors.lastname: Huang
authors.affiliation: Department of Pharmacology, National Defense Medical Center, Taipei, Taiwan, R.O.C.; Department of Pharmacology, Taipei Medical University, Taipei, Taiwan, R.O.C.
authors.forename: Chin-Chen
authors.initials: CC
authors.lastname: Wu
mesh_terms: D000138:Acidosis / Q000517:prevention & control; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D062186:Arterial Pressure / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D004195:Disease Models, Animal; D058492:Drug Repositioning; D007275:Injections, Intravenous; D015850:Interleukin-6 / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D020556:Neutrophil Infiltration / Q000187:drug effects; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000378:metabolism; D010538:Peritonitis / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D012642:Selegiline / Q000494:pharmacology*; D018805:Sepsis / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D013481:Superoxides / Q000378:metabolism; D016019:Survival Analysis; D000093242:Interleukin-6 Inhibitors
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D053148:Caspase 3; D015850:Interleukin-6; D018696:Neuroprotective Agents; D052247:Nitric Oxide Synthase Type II; D012642:Selegiline; D013481:Superoxides; D000093242:Interleukin-6 Inhibitors; C496318:Nos2 protein, rat