Stobadine attenuates impairment of an intestinal barrier model caused by 4-hydroxynonenal.
Alterations in the intestinal barrier permeability occur in a broad spectrum of abdominally related pathologies, mostly due to disturbed oxidative homeostasis and increased lipid peroxidation. 4-Hydroxynonenal (HNE), a major lipid peroxidation product, is physiologically present in healthy gastric mucosa, but is increased in early stages of colon cancer and patients with duodenal peptic ulcer. Nevertheless, such supraphysiological levels of HNE have not yet been associated with increased intestinal permeability, even though, as we have described in this paper, they could play important role. In vitro model of intestinal barrier was established by growing Caco-2 cell line on cell culture permeable inserts. The pyridoindole derivative stobadine in hydrophilic and lipophilic form was used for barrier model protection. Both forms of stobadine were able to prevent damaging HNE effects, and reduce generation of reactive oxygen species and permeability of the intestinal barrier. Immunocytochemical analysis has confirmed beneficial effect of stobadine in reducing the formation of HNE-protein conjugates in the cells. Lipophilic form of stobadine proved to be more efficient than hydrophilic, implying importance of lipids in maintaining barrier function. The results obtained indicate that HNE might be important factor affecting intestinal barrier integrity, while stobadine could efficiently protect intestinal cells against harmful HNE effects.
Department of Pathology, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia. marinac@irb.hr
Marina
M
Cindric
Ana
A
Cipak
Emilija
E
Zapletal
Morana
M
Jaganjac
Lidija
L
Milkovic
Georg
G
Waeg
Svorad
S
Stolc
Neven
N
Zarkovic
Sunjic
S
Suzana Borovic
D000111:Acetylcysteine / Q000494:pharmacology; D000447:Aldehydes / Q000633:toxicity*; D000975:Antioxidants / Q000494:pharmacology*; D018938:Caco-2 Cells; D002243:Carbolines / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002839:Chromans / Q000494:pharmacology; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D015227:Lipid Peroxidation; D010539:Permeability; D017382:Reactive Oxygen Species / Q000378:metabolism
D000447:Aldehydes; D000975:Antioxidants; D002243:Carbolines; D002839:Chromans; D017382:Reactive Oxygen Species; C027576:4-hydroxy-2-nonenal; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid; D000111:Acetylcysteine; C100106:dicarbine