Post-treatment with N-acetylcysteine ameliorates endotoxin shock-induced organ damage in conscious rats.
N-acetylcysteine (NAC) is an antioxidant and cytoprotective agent with scavenging action against reactive oxygen species and inhibitory effects on pro-inflammatory cytokines. In a previous study, we found that pretreatment with NAC attenuated organ dysfunction and damage, reduced the production of free radicals, tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) following endotoxemia elicited by administration of lipopolysaccharide (LPS). In the present study, we tested the effects of post-treatment with NAC on the sepsis-induced change. Post-treatment imitates clinical therapeutic regimen with administration of drug after endotoxemia. Endotoxin shock was induced by intravenous injection of Klebsiella pneumoniae LPS (10 mg/kg) in conscious rats. Mean arterial pressure (MAP) and heart rate (HR) were continuously monitored for 48 h after LPS administration. NAC was given 20 min after LPS. Measurements of biochemical substances were taken to reflect organ functions. Biochemical factors included blood urea nitrogen (BUN), creatinine (Cre), lactate dehydrogenase (LDH), creatine phosphokinase (CPK), aspartate transferase (GOT), alanine transferase (GPT), TNF-alpha, interleukin-6 (IL-6), and interleukin-10 (IL-10). LPS significantly increased blood BUN, Cre, LDH, CPK, GOT, GPT, TNF-alpha, IL-6, IL-10 levels and HR, and decreased MAP. Post-treatment with NAC diminished the decrease in MAP, increased the HR, and decreased the markers of organ injury (BUN, Cre, LDH, CPK, GOT, GPT) and inflammatory biomarkers (TNF-alpha, IL-6, IL-10) after LPS. We conclude that post-treatment with NAC suppresses the release of plasma TNF-alpha, IL-6, and IL-10 in endotoxin shock, and decreases the markers of organ injury. These beneficial effects protect against LPS-induced kidney, heart and liver damage in conscious rats. The beneficial effects may suggest a potential chemopreventive effect of this compound after sepsis.
Hsu
Bang-Gee
BG
Department of Nephrology, Buddhist Tzu Chi General Hospital, Hualien, Taiwan.
Lee
Ru-Ping
RP
Yang
Fwu-Lin
FL
Harn
Horng-Jyh
HJ
Chen
Hsing I
HI
D000111:Acetylcysteine / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D004334:Drug Administration Schedule; D016166:Free Radical Scavengers / Q000008:administration & dosage / Q000627:therapeutic use*; D006321:Heart / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D007677:Kidney Function Tests; D008070:Lipopolysaccharides; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008111:Liver Function Tests; D008297:Male; D009102:Multiple Organ Failure / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D009206:Myocardium / Q000473:pathology; D051381:Rats; D011921:Rats, Inbred WKY; D012772:Shock, Septic / Q000139:chemically induced / Q000150:complications / Q000473:pathology / Q000503:physiopathology
D016207:Cytokines; D016166:Free Radical Scavengers; D008070:Lipopolysaccharides; D000111:Acetylcysteine