Prostaglandins, Leukotrienes and Essential Fatty Acids 72 (2005) 41–47 The significance of oxidant/antioxidant balance for the pathogenesis of experimental sepsis by multidrug-resistant Pseudomonas aeruginosa Vassilios Koussoulas a , Evangelos J. Giamarellos-Bourboulis b,Ã , Theodoros Adamis c , Maria Mouktaroudi c , Lambros Sabracos c , Despina Perrea c , Helen Giamarellou b , Amalia Dionyssiou-Asteriou a a Department of Biological Chemistry, Medical School, University of Athens, Greece b 4th Department of Internal Medicine, Attikon University Hospital, 1 Rimini Street, 124 64 Athens, Greece c Laboratory of Experimental Surgery and Surgical Research, Medical School, University of Athens, Greece Received 29 May 2004; accepted 1 September 2004 Abstract Objective: The significance of lipid peroxidation as an independent factor leading to sepsis by multidrug-resistant Pseudomonas aeruginosa. Design experimental study Methods: Twenty-six rabbits were applied. They were divided into two groups; A (n ¼ 6) comprising controls, and B (n ¼ 20) comprising animals infected by the injection of 1  10 8 cfu/kg inoculum of the test pathogen into the left inner jugular vein. Six rabbits of group B were followed-up to estimate survival; all of the remaining were sacrificed. Blood was sampled for the determination of serum malondialdehyde (MDA) by the thiobarbiturate assay, total antioxidant status (TAS) by a chromogenic assay, tumor necrosis factor alpha by a bioassay on fibrosarcoma L929 cell line, and endotoxins (LPS) by the QCL-1000 LAL assay. Results: Mean survival of group B was 60.0715.8h. MDA was significantly higher in group B compared to group A at 30, 60, 120 and 150 min. TAS was statistically decreased in group B compared to group A at 30 and 60min. Increases of MDA in group B were followed by reciprocal decreases of TAS (P of correlation o0.001). Hemodynamic instability was recorded in group B compared to group A 160 min after bacterial challenge. Conclusions: Early alterations of oxidant/antioxidant balance occur in experimental sepsis by multidrug-resistant P. aeruginosa followed by hemodynamic instability. Results highlight the perspective of the administration of antioxidants as immunomodulatory treatment of sepsis in animal studies. r 2004 Elsevier Ltd. All rights reserved. 1. Introduction Peroxidation of polyunsaturated fatty acids em- bedded in plasma membrane phospholipids is consid- ered as a mechanism often implicated in the septic process [1–3]. However, data on the significance of these alterations in the series of events leading to sepsis are lacking. Since the incidence of nosocomial sepsis by multidrug-resistant isolates has been seriously increased over the last decade, immunomodulatory treatment appears as an attractive alternative for therapy [4]. Lipid peroxidation might be a target for immunomo- dulation; so its contribution on the pathogenesis of sepsis needs to be further clarified. The present study was focused on experimental sepsis by multidrug-resistant Pseudomonas aeruginosa. Its main issue was to investigate the exact implication of ARTICLE IN PRESS www.elsevier.com/locate/plefa 0952-3278/$-see front matter r 2004 Elsevier Ltd. All rights reserved. doi:10.1016/j.plefa.2004.09.003 Ã Corresponding author. Tel.: +302105831994; fax: +302105326446. E-mail address: giamarel@internet.gr (E.J. Giamarellos-Bourboulis).