Prophylaxis against lipopolysaccharide-induced liver injuries by lipoic acid in rats.
Lipopolysaccharide (LPS) is a major cell wall molecule of Gram-negative bacteria known to stimulate the synthesis and secretion of several metabolites, such as reactive oxygen species, from phagocytes that play an important role in the pathogenesis of tissue injuries. In this study, the prophylactic effect of the antioxidant lipoic acid was evaluated in an animal acute organ injury model. Animals were pre-treated intraperitoneally with lipoic acid (50 mg kg(-1) body weight) or saline; 3 h later, pretreated animals were challenged intravenously with LPS (Escherichia coli 0111:B4, 1.0 mg kg(-1) body weight) or saline and killed 21 h later. Saline-pretreated animals challenged with LPS were extensively damaged in the liver, as evidenced by an increase in plasma alanine and aspartate aminotransferase activities. Also, LPS injection to saline-pretreated animals resulted in significant increases in plasma tumour necrosis factor-alpha (TNFalpha) and nitric oxide (NO) concentrations, suggestive of activation of the proinflammatory response. The LPS challenge to saline-pretreated animals also increased hepatic myeloperoxidase activity as well as protease and chloramine levels, suggestive of neutrophil infiltration and activation of the inflammatory response. In addition, the involvement of oxidative stress was evident, because a significant increase in lipid peroxidation was observed in the livers of saline-pretreated animals challenged with LPS. The administration of lipoic acid prior to LPS challenge resulted in a significant alleviation of liver injuries, evidenced by a general reversal of the altered biochemical indices toward normal among treated animals. These results indicate that lipoic acid may serve as a potentially effective prophylactic pharmacological agent in alleviating LPS-induced tissue injuries.
Suntres
Zacharias E
ZE
Health Hazards Group, Operational Medicine Section, Defence Research and Development Canada-Toronto, 1133 Sheppard Avenue West, Toronto, Ont, Canada M3M 3B9. Zach.Suntres@drdc-rddc.gc.ca
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D056486:Chemical and Drug Induced Liver Injury; D002700:Chloramines / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D010450:Endopeptidases / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008070:Lipopolysaccharides / Q000008:administration & dosage* / Q000633:toxicity; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008107:Liver Diseases / Q000097:blood / Q000517:prevention & control*; D008297:Male; D009569:Nitric Oxide / Q000097:blood; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D008063:Thioctic Acid / Q000494:pharmacology / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D002700:Chloramines; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D008063:Thioctic Acid; D009195:Peroxidase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D010450:Endopeptidases; C030816:chloramine