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  • The effect of clodronate on the integrity and viability of rat small intestine in Vitro-A comparison with EDTA
    Žakelj, Simon ; Vadnjal, Lea ; Kristl, Albin
    Although substances, which can increase the paracellular permeability of intestinal mucosa, could be very helpful for increasing the bioavailability ofhydrophilic drugs, they are not used ... therapeutically due to the possibilities of acute or long-term toxicity (intestinal inflammations due to penetration of bacterial fragments into subepithelial spaces). In this paper the abilities of a calcium chelator EDTA and clodronate (a first generation bisphosphonate) to increase the paracellular permeability were assessed using rat jejunum in side-by-side diffusion chambers while the viability of the tissue was monitored by transepithelial potential difference. Although clodronate is less potent than EDTA in depleting calcium from the intestinal tissue, it significantly increased the paracellular permeability of viable ratjejunum Ćin vitroĆ when tested at 15mM and higher concentrations (the highest therapeutic dose dissolved in 250 ml gives a 22mM solution of clodronate). This effect was reversible under Ćhigh-calciumĆ conditions. Sinceclodronate therapy does not have any long-term consequences it was concluded that a safe, transient increase of small intestinal permeability is possible. However, the acute gastrointestinal undesired effects, which can develop during the therapy with high doses of clodronate, might also occur after oral applications of paracellular permeability enhancers. Namely, 30mM and higher concentrations of clodronate caused a loss of the tissue viability in all rat jejunal segments tested in Ćin vitroĆ conditions. A similar effect was observed with much lower concentrations of EDTA.
    Vir: Biological & pharmaceutical bulletin. - ISSN 0918-6158 (vol. 28, no. 7, 2005, str. 1249-1253)
    Vrsta gradiva - članek, sestavni del
    Leto - 2005
    Jezik - angleški
    COBISS.SI-ID - 1816433

vir: Biological & pharmaceutical bulletin. - ISSN 0918-6158 (vol. 28, no. 7, 2005, str. 1249-1253)

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