Membrane peroxidation by lipopolysaccharide and iron-ascorbate adversely affects Caco-2 cell function: beneficial role of butyric acid.
BACKGROUND
Membrane lipid peroxidation may play a role in immune-mediated bowel diseases.


OBJECTIVE
We examined the effects of lipopolysaccharide (LPS), a ubiquitous endotoxin mediator of gram-negative bacteria, alone and in combination with iron-ascorbate, on enterocyte function. Furthermore, we assessed the antioxidant capacity of butylated hydroxytoluene (BHT) and butyric acid, which are known to play a significant role in the welfare of intestinal mucosa.


METHODS
Differentiated intestinal Caco-2 cells were used to study the induction of membrane peroxidation by LPS (100 micro g/mL) and iron-ascorbate (0.2 and 2 mmol/L, respectively) and to examine the beneficial effects of BHT and butyric acid.


RESULTS
A significant dose-dependent increase in malondialdehyde, accompanied by lower apical membrane fluidity and significantly decreased sucrase activity, was observed when Caco-2 cells were incubated with LPS. LPS also augmented paracellular permeability ([(14)C]polyethylene glycol flux), prostaglandin E(2) production, and cyclooxygenase-2 (EC 1.14.99.1) expression. These abnormalities were exacerbated by the coadministration of iron-ascorbate, but most of them were suppressed by butyric acid and BHT.


CONCLUSIONS
Bacterial endotoxin and prooxidants may overwhelm antioxidant defenses and become deleterious to enterocyte function, whereas butyric acid and BHT may provide antioxidant protection.
Courtois
Frederic
F
Division of Gastroenterology, Hepatology, and Nutrition, Centre de Recherche, Sainte Justine Hospital and the Department of Nutrition, Université de Montréal, Montreal, Québec, Canada.
Seidman
Ernest G
EG
Delvin
Edgard
E
Asselin
Claude
C
Bernotti
Sandra
S
Ledoux
Marielle
M
Levy
Emile
E
D000975:Antioxidants / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology; D002084:Butylated Hydroxytoluene / Q000494:pharmacology*; D020148:Butyric Acid / Q000494:pharmacology*; D018938:Caco-2 Cells / Q000378:metabolism / Q000502:physiology; D002463:Cell Membrane Permeability / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000096:biosynthesis; D020895:Enterocytes / Q000502:physiology; D006801:Humans; D007527:Isoenzymes / Q000096:biosynthesis; D015227:Lipid Peroxidation / Q000187:drug effects*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008315:Malondialdehyde / Q000032:analysis; D008560:Membrane Fluidity / Q000187:drug effects; D008563:Membrane Lipids / Q000378:metabolism; D008565:Membrane Proteins; D010084:Oxidation-Reduction; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis; D013393:Sucrase / Q000037:antagonists & inhibitors / Q000378:metabolism
D000975:Antioxidants; D007527:Isoenzymes; D008070:Lipopolysaccharides; D008563:Membrane Lipids; D008565:Membrane Proteins; D020148:Butyric Acid; D002084:Butylated Hydroxytoluene; D008315:Malondialdehyde; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D013393:Sucrase; D015232:Dinoprostone; D001205:Ascorbic Acid