The induction of lipid peroxidation by E. coli lipopolysaccharide on rat hepatocytes as an important factor in the etiology of endotoxic liver damage.
Oxygen-derived radicals have been suggested to produce tissue injury during endotoxic shock by initiating lipid peroxidation. In order to investigate the induction of lipid peroxidation by Escherichia coli 0111:B4 lipopolysaccharide (LPS) on hepatocytes, malondialdehyde (MDA) and superoxide dismutase (SOD) activity have been evaluated in vivo and in vitro using two experimental models: rat liver after the establishment of endotoxic reversible shock, and cultured hepatocytes after treatment with LPS. Liver MDA levels were increased in vivo during the acute-phase of endotoxic shock, decreasing below control values in the recovery phase. An inverse pattern was obtained when SOD activity was measured, consistent with an active system of cellular protection. Similar results were obtained in vitro after treatment of cultured hepatocytes with LPS (50 micrograms/ml), thus indicating that a direct LPS cytotoxic effect on hepatocytes exits during the endotoxic process. The direct LPS interaction induced alterations in Ca2+ permeability of hepatocyte plasma membrane as detected by flow cytometry using the fluorescent probe Indo-1.
Portolés
M T
MT
Department of Biochemistry and Molecular Biology, Faculty of Chemistry, Universidad Complutense, Madrid, Spain.
Ainaga
M J
MJ
Pagani
R
R
D000818:Animals; D002118:Calcium / Q000032:analysis; D002478:Cells, Cultured; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology; D004790:Enzyme Induction / Q000187:drug effects; D004926:Escherichia coli; D005434:Flow Cytometry; D015227:Lipid Peroxidation; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D012772:Shock, Septic / Q000209:etiology; D013482:Superoxide Dismutase / Q000096:biosynthesis
D008070:Lipopolysaccharides; D008315:Malondialdehyde; D013482:Superoxide Dismutase; D002118:Calcium