Details

Autor(en) / Beteiligte

• Cindric, Marina
• Cipak, Ana
• Zapletal, Emilija
• Jaganjac, Morana
• Milkovic, Lidija
• Waeg, Georg
• Stolc, Svorad
• Zarkovic, Neven
• Suzana Borovic, Sunjic

Titel

Stobadine attenuates impairment of an intestinal barrier model caused by 4-hydroxynonenal

Ist Teil von

• Toxicology in vitro, 2013-02, Vol.27 (1), p.426-432

Ort / Verlag

England: Elsevier Ltd

Erscheinungsjahr

2013

Quelle

Access via ScienceDirect (Elsevier)

Beschreibungen/Notizen

• ► Establishment of an in vitro intestinal barrier model for studying lipid peroxidation. ► Revealing 4-hydroxynonenal as a causative factor of intestinal barrier impairment. ► Prevention of HNE damaging effects by hydrophilic or lipophilic form of stobadine. ► Stobadine dipalmitate prevented HNE toxicity and reduced barrier permeability. 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.