oleic acid enhance absorption of mitoxantrone through monolayers of caco-2 cells
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doi:10.1016/j.toxlet.2011.05.491
138 Abstracts / Toxicology L
1255robiotic strain Lactobacillus casei does not markedly alter rat
iver microsomal cytochromes P450
. Anzenbacher 1,∗, E. Anzenbacherova 2, Z. Matuskova 1,
. Zidek 3, H. Tlaskalova-Hogenova 4
Pharmacology, Palacky University at Olomouc, Faculty of Medicinend Dentistry, Olomouc, Czech Republic, 2 Medical Chemistry andiochemistry, Palacky University at Olomouc, Faculty of Medicinend Dentistry, Olomouc, Czech Republic, 3 Institute of Experimentaledicine, Academy of Sciences of the Czech Republic, Praha, Czech
epublic, 4 Institute of Microbiology, Academy of Sciences of thezech Republic, Praha, Czech Republic
Although the probiotics are widely used in human diet, there islack of information on their possible effects on drug metabolism.
n this presentation we investigated the influence of a probioticactobacillus casei on expression and activities of rat liver microso-al cytochromes P450 (CYP). Suspension of live Lactobacillus casei
L. casei) was applied intragastically for seven consecutive dayso male Wistar rats (9 × 108 CFU/dose, N = 6). Control group (N = 6)as given the same volume of physiological solution. In the livericrosomal fraction of each animal, protein expression of CYP1A1,
YP2B1/2, 2C6, 2C11, 2E1 and CYP3A was examined by Westernlotting with the use of specific antibodies. Data were analysed byensitometry. In parallel, formation of warfarin metabolites wasollowed in the same samples (warfarin is known to be metabolizedy various rat liver CYP enzymes in a rather specific way). Analy-es were performed by HPLC (Ishizuka M., et al., DMD 35 (2007)2). The results did not reveal marked differences in the expres-ion and activity of the individual liver microsomal CYP forms. Aendency to higher expression after the administration of probioticas observed for CYP2C11; on the other hand, an opposite effectas traced in case of CYP2E1 and CYP1A1 form. The interindividual
ariability in activities and expression patterns contributed signifi-antly to the final result showing no differences which might causeprominents effect of probiotics on drug metabolism in the rat livery CYP forms examined.
Supported by GACR 305/08/535, MSM6198959216 and IGAPOL LF2011-005 projects.
oi:10.1016/j.toxlet.2011.05.489
1256leic acid enhance absorption of mitoxantrone throughonolayers of Caco-2 cells
. Aspenström-Fagerlund 1,∗, E. Netzel 2, N. Ilbäck 1, J. Tallkvist 3,
. Glynn 1
Risk Benefit Assessment Department, National Food Administration,ppsala, Sweden, 2 National Food Administration, Uppsala, Sweden,Swedish University of Agricultural Sciences, Department ofiomedical Sciences and Veterinary Public Health, Uppsala, Sweden
An important efflux transporter protein for toxicants in food ishe human breast cancer resistance protein (BCRP/ABCG2). BCRP
ediated efflux decreases absorption of for example heterocyclicmines (PhIP), mycotoxins (aflatoxin B1), human and veterinaryrugs (fluoroquinolones, mitoxantrone (MXR) and benzimida-
oles). It has been shown that fat rich food can increase absorptionf substances normally transported by another efflux transporterrotein, para-glukoprotein. We hypothesize that fatty acids in foodnfluence the function of BCRP resulting in an increased absorption
205S (2011) S60–S179
of food toxicans. We investigated if the most common fatty acidin food, oleic acid (OA), with or without the BCRP inhibitor Ko143,increases the absorption of MXR, a known substrate for BCRP, inCaco-2 cell monolayers. Caco-2 cell monolayers were differentiatedon permeable filters placed in bicameral chambers before exposureto 3H-MXR in OA emulsions (1–5 mM) or emulsions of oleic acid (1,2 mM) combined with Ko143. We also investigated if gene expres-sion of BCRP was influenced by OA (1 mM) exposure for 0, 1.5, 3, 6and 9 h. BCRP protein was quantified with Western Blot in Caco-2cells after oleic acid (1 mM) exposure for 1.5 and 6 h. OA signifi-cantly increased the absorption of MXR but when Ko143 and oleicacid were combined, the effect on MXR absorption was less pro-nounced. Gene expression of BCRP was increased after 3, 6 and 9 hof OA exposure but the amount of BCRP protein was not influencedby OA up to 6 h exposure for OA.
doi:10.1016/j.toxlet.2011.05.490
P1257Determination of organochlorine pesticide residue levels, inproduced bottled drinking water in Ahvaz City, Iran
A. Behfar 1,∗, Z. Nazari Khorasgani 2, Z. Esmaeily 1
1 Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran,2 Toxicology & Pharmacology, Ahvaz Jundishapur University ofMedical Sciences, Ahvaz, Iran
Purpose: In recent years the use of bottled water has increasedin Iran. But such waters are not monitored regularly and there isextremely limited data on chemical composition in them. In orderto separation and quantification of selected organochlorine pes-ticide residues (OCs) [op’DDT, pp’DDT, op’ DDD, pp’DDD, pp’DDE,op’ DDE, Alderin, Dieldrin, Heptachlor, Heptachlor (Exo, Endo), (�,�, �, �) HCH, (�, �)endosulfan and metoxychlor] of produced bot-tled drinking water of Anahita factory in Ahvaz City this work wasdone. Methods: For this purpose 6 times, each time, one compositesamples from water of a factory which comprising 20 grab sampleswas taken, acidified to pH 2 (in situ). 1 L of each water sample wasextracted with 15 ml CH2Cl2 (3 times), concentrated (using a rotaryvacuum evaporator) and transferred into a conditioned chromatog-raphy column packed with silica gel. Then the column was elutedwith 20 ml CH2Cl2. The elution solvent was concentrated to dryness(by rotary vacuum evaporator). Finally, the residue was dissolvedin 2 ml Hexan and by injection 1 mg of that into the gas chro-matograph equipped with a micro electron capture detector wasanalyzed. Results: pp’DDD, �HCH, op’DDE and �-endosulfan of the18 selected OCs were not detected in all of the investigated watersamples. The highest and lowest mean concentration of 18 investi-gated pesticides belonged to �-HCH and dieldrin with 0.0441 mg/land 0.0018 mg/l respectively. All detected OCs in bottled waters