Adjuvant potential of selegiline in attenuating organ dysfunction in septic rats with peritonitis

Cheng-Ming Tsao; Jhih-Gang Jhang; Shiu-Jen Chen; Shuk-Man Ka; Tao-Cheng Wu; Wen-Jinn Liaw; Hsieh-Chou Huang; Chin-Chen Wu

doi:10.1371/journal.pone.0108455

Adjuvant potential of selegiline in attenuating organ dysfunction in septic rats with peritonitis

PLoS One. 2014 Sep 30;9(9):e108455. doi: 10.1371/journal.pone.0108455. eCollection 2014.

Authors

Cheng-Ming Tsao¹, Jhih-Gang Jhang², Shiu-Jen Chen³, Shuk-Man Ka⁴, Tao-Cheng Wu⁵, Wen-Jinn Liaw⁶, Hsieh-Chou Huang⁷, Chin-Chen Wu⁸

Affiliations

¹ 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.
² Department of Pharmacology, National Defense Medical Center, Taipei, Taiwan, R.O.C.
³ 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.
⁴ Graduate Institute of Aerospace and Undersea Medicine, National Defense Medical Center, Taipei, Taiwan, R.O.C.
⁵ 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.
⁶ 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.
⁷ Department of Anesthesiology, Cheng-Hsin General Hospital, Taipei, Taiwan, R.O.C.
⁸ Department of Pharmacology, National Defense Medical Center, Taipei, Taiwan, R.O.C.; Department of Pharmacology, Taipei Medical University, Taipei, Taiwan, R.O.C.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Acidosis / prevention & control
Animals
Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
Arterial Pressure / drug effects
Caspase 3 / metabolism
Disease Models, Animal
Drug Repositioning
Injections, Intravenous
Interleukin-6 / antagonists & inhibitors
Interleukin-6 / metabolism
Kidney / drug effects
Kidney / metabolism
Kidney / pathology
Liver / drug effects
Liver / metabolism
Liver / pathology
Lung / drug effects
Lung / metabolism
Lung / pathology
Male
Neuroprotective Agents / pharmacology*
Neutrophil Infiltration / drug effects
Nitric Oxide Synthase Type II / antagonists & inhibitors
Nitric Oxide Synthase Type II / metabolism
Peritonitis / drug therapy*
Peritonitis / metabolism
Peritonitis / mortality
Peritonitis / pathology
Rats
Rats, Wistar
Selegiline / pharmacology*
Sepsis / drug therapy*
Sepsis / metabolism
Sepsis / mortality
Sepsis / pathology
Superoxides / metabolism
Survival Analysis

Substances

Anti-Inflammatory Agents, Non-Steroidal
Interleukin-6
Neuroprotective Agents
Superoxides
Selegiline
Nitric Oxide Synthase Type II
Nos2 protein, rat
Caspase 3

Grants and funding

This work supported by grants from National Science Council, Taiwan, R.O.C. (NSC 97-2320-B-016-006-MY3, 98-2314-B-075-005-MY3 and 100-2320-B-016-008) and Cheng Hsin General Hospital, Taiwan, R.O.C. (CHGH 99-61). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.