title: Rosiglitazone ameliorates endotoxin-induced organ damage in conscious rats.
abstract: Rosiglitazone is a peroxisome proliferator-activated receptor (PPAR)-γ agonist. By inhibiting nuclear factor κB (NF-κB), it decreases tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6) and has an anti-inflammatory effect. Endotoxin shock can induce the production of several inflammatory mediators such as TNF-α and IL-6, leading to multiple organ dysfunction and death. We investigated the effects of rosiglitazone (.3 mg/kg, intravenous administration) on the physiologic attributes and cytokine levels in endotoxin shock in conscious rats. Endotoxin shock was induced by intravenous injection of Klebsiella pneumoniae lipopolysaccharides (LPSs; 10 mg/kg) in conscious rats. Mean arterial pressure (MAP) and heart rate (HR) were continuously monitored for 24 hr after LPS administration. Levels of biochemical and cytokine parameters, including glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), blood urea nitrogen (BUN), creatinine (Cre), lactic dehydrogenase (LDH), creatine phosphokinase (CPK), glucose, TNF-α, and IL-6 were measured at 0, 1, 3, 6, 12, and 24 hr after sepsis. Endotoxin shock significantly increased blood GOT, GPT, BUN, Cre, LDH, CPK, glucose, TNF-α, and IL-6 levels and HR, while also decreasing MAP. Rosiglitazone diminished the increase in HR, decreased the markers of organ injury (GOT, GPT, BUN, Cre, LDH, CPK, glucose) and inflammatory biomarkers (TNF-α, IL-6), and did not affect MAP after LPS. In conclusion, rosiglitazone ameliorated endotoxin shock-induced markers of organ injury and suppressed the release of TNF-α and IL-6 in conscious rats.
authors.affiliation: Institute of Medical Sciences, Tzu Chi University, No. 701 Section 3 Chung Yang Rd., Hualien, Taiwan.
authors.forename: Wen-Tien
authors.initials: WT
authors.lastname: Wu
authors.forename: Chia-Chi
authors.initials: CC
authors.lastname: Lee
authors.forename: Chung-Jen
authors.initials: CJ
authors.lastname: Lee
authors.forename: Yi-Maun
authors.initials: YM
authors.lastname: Subeq
authors.forename: Ru-Ping
authors.initials: RP
authors.lastname: Lee
authors.forename: Bang-Gee
authors.initials: BG
authors.lastname: Hsu
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001219:Aspartate Aminotransferases / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects; D001806:Blood Urea Nitrogen; D003243:Consciousness; D003402:Creatine Kinase / Q000097:blood; D006339:Heart Rate / Q000187:drug effects; D015850:Interleukin-6 / Q000097:blood; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D051381:Rats; D011921:Rats, Inbred WKY; D000077154:Rosiglitazone; D012772:Shock, Septic / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D045162:Thiazolidinediones / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D000893:Anti-Inflammatory Agents; D015850:Interleukin-6; D008070:Lipopolysaccharides; D045162:Thiazolidinediones; D014409:Tumor Necrosis Factor-alpha; D000077154:Rosiglitazone; D007770:L-Lactate Dehydrogenase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D003402:Creatine Kinase