It is recognized that mycotoxins can cause a variety of adverse health effects in animals, including altered gastrointestinal barrier function. It is the aim of the present study to determine whether mycotoxin-contaminated diets can alter the oral bioavailability of the antibiotics doxycycline and paromomycin in pigs, and whether a mycotoxin adsorbing agent included into diets interacts with those antibiotics. Experiments were conducted with pigs utilizing diets that contained blank feed, mycotoxin-contaminated feed (T-2 toxin or deoxynivalenol), mycotoxin-contaminated feed supplemented with a glucomannan mycotoxin binder, or blank feed supplemented with mycotoxin binder. Diets with T-2 toxin and binder or deoxynivalenol and binder induced increased plasma concentrations of doxycycline administered as single bolus in pigs compared to diets containing blank feed. These results suggest that complex interactions may occur between mycotoxins, mycotoxin binders, and antibiotics which could alter antibiotic bioavailability. This could have consequences for animal toxicity, withdrawal time for oral antibiotics, or public health.
References
[1]
Monbaliu, S.; van Poucke, C.; Detavernier, C.; Dumoulin, F.; van de Velde, M.; Schoeters, E.; van Dyck, S.; Averkieva, O.; van Peteghem, C.; de Saeger, S. Occurrence of mycotoxins in feed as analyzed by a multi-mycotoxin LC-MS/MS method. J. Agric. Food Chem. 2010, 58, 66–71, doi:10.1021/jf903859z. 19994896
[2]
Hussein, H.S.; Brasel, J.M. Toxicity, metabolism, and impact of mycotoxins on humans and animals. Toxicology 2001, 167, 101–134, doi:10.1016/S0300-483X(01)00471-1.
Mahfoud, R.; Maresca, M.; Garmy, N.; Fantini, J. The mycotoxin patulin alters the barrier function of the intestinal epithelium: Mechanism of action of the toxin and protective effects of glutathione. Toxicol. Appl. Pharmacol. 2002, 181, 209–218, doi:10.1006/taap.2002.9417. 12079430
[5]
Maresca, M.; Mahfoud, R.; Pfohl-Leszkowicz, A.; Fantini, J. The mycotoxin ochratoxin A alters intestinal barrier and absorption functions but has no effect on chloride secretion. Toxicol. Appl. Pharmacol. 2001, 176, 54–63, doi:10.1006/taap.2001.9254. 11578148
[6]
Maresca, M.; Mahfoud, R.; Garmy, N.; Fantini, J. The mycotoxin deoxynivalenol affects nutrient absorption in human intestinal epithelial cells. J. Nutr. 2002, 132, 2723–2731. 12221236
[7]
McLaughlin, J.; Padfield, P.J.; Burt, J.P.; O’Neill, C.A. Ochratoxin A increases permeability through tight junctions by removal of specific claudin isoforms. Am. J. Physiol. Cell Physiol. 2004, 287, C1412–C1417, doi:10.1152/ajpcell.00007.2004. 15229101
[8]
Sergent, T.; Parys, M.; Garsou, S.; Pussemier, L.; Schneider, Y.J.; Larondelle, Y. Deoxynivalenol transport across human intestinal Caco-2 cells and its effects on cellular metabolism at realistic intestinal concentrations. Toxicol. Lett. 2006, 164, 167–176, doi:10.1016/j.toxlet.2005.12.006. 16442754
Hunder, G.; Schumann, K.; Strugala, G.; Gropp, J.; Fichtl, B.; Forth, W. Influence of subchronic exposure to low dietary deoxynivalenol, a trichothecene mycotoxin, on intestinal absorption of nutrients in mice. Food Chem. Toxicol. 1991, 29, 809–814, doi:10.1016/0278-6915(91)90107-I.
[11]
Subramanian, S.; Balasubramanian, N.; William, S.; Govindasamy, S. In vivo absorption of 14C-glucose and 14C-glycine by the rat intestine during ochratoxin A toxicosis. Biochem. Int. 1991, 23, 655–661. 1831359
[12]
Jouany, J.P. Methods for preventing, decontaminating and minimizing the toxicity of mycotoxins in feeds. Anim. Feed. Sci. Technol. 2007, 137, 342–362, doi:10.1016/j.anifeedsci.2007.06.009.
[13]
Kabak, B.; Dobson, A.D. Biological strategies to counteract the effects of mycotoxins. J. Food Prot. 2009, 72, 2006–2016. 19777908
[14]
Avantaggiato, G.; Solfrizzo, M.; Visconti, A. Recent advances on the use of adsorbent materials for detoxification of Fusarium mycotoxins. Food Addit. Contam. 2005, 22, 379–388, doi:10.1080/02652030500058312. 16019808
[15]
Ledoux, D.R.; Rottinghous, G.E.; Bermudez, A.J. In vitro Binding of Mycotoxins by Adsorbents Does Not Always Translate into in Vivo Efficacy. In Mycotoxins and Phycotoxins in Perspective at the Turn of the Millennium; Koe, W.J., Samson, R.A., van Egmond, H.P., Gilbert, J., Sabino, M., Eds.; IUPAC: Wageningen, The Netherlands, 2001; pp. 279–287.
[16]
European Commission. Commission Regulation No 386/2009 of 12 May 2009 amending Regulation (EC) No 1831/2003 of the European Parliament and of the Council as regards the establishment of a new functional group of feed additives. Off. J. Eur. Union 2009, L 118, 66.
[17]
EFSA. Statement on the establishment of guidelines for the assessment of additives from the functional group ‘substances for reduction of the contamination of feed by mycotoxins’. EFSA J. 2010, 8.
[18]
Amer, A.M.M. Pharmacokinetic Interaction between Antibiotics and Antimycotoxins in Broiler Chickens, Proceeding of 14th World Veterinary Poultry Congress, Istanbul, Turkey, 22–26 August 2005.
[19]
Suspected drug adverse reactions reported to The Bureau of Veterinary Drugs. Can. Vet. J. 1992, 33, 237–244. 17423982
[20]
Shryock, T.R.; Klink, P.R.; Readnour, R.S.; Tonkinson, L.V. Effect of bentonite incorporated in a feed ration with tilmicosin in the prevention of induced mycoplasma gallisepticum airsacculitis in broiler chickens. Avian Dis. 1994, 38, 501–505, doi:10.2307/1592071. 7832702
[21]
EFSA. Scientific Opinion on the safety and efficacy of bentonite (dioctahedral montmorillonite) as feed additive for all species. EFSA J. 2011, 9.
Calvert, T.W.; Aidoo, K.E.; Candlish, A.G.; Fuat, A.R. Comparison of in vitro cytotoxicity of Fusarium mycotoxins, deoxynivalenol, T-2 toxin and zearalenone on selected human epithelial cell lines. Mycopathologia 2005, 159, 413–419, doi:10.1007/s11046-005-0254-4.
[24]
European Commission. Commission Recommendation 576/2006/EC of 17 August 2006 on the presence of deoxynivalenol, zearalenone, ochratoxin A, T-2 and HT-2 and fumonisins in products intended for animal feeding. Off. J. Eur. Union 2006, L229, 7.
[25]
Bottalico, A.; Perrone, G. Toxigenic Fusarium species and mycotoxins associated with head blight in small-grain cereals in Europe. Eur. J. Plant Pathol. 2002, 108, 611–624, doi:10.1023/A:1020635214971.
Baert, K.; Croubels, S.; Gasthuys, F.; de Busser, J.; de Backer, P. Pharmacokinetics and oral bioavailability of a doxycycline formulation (doxycycline 75%) in nonfasted young pigs. J. Vet. Pharmacol. Ther. 2000, 23, 45–48, doi:10.1046/j.1365-2885.2000.00235.x. 10747242
[28]
European Commission. Commision Decision 2002/657/EC implementing Council Directive 96/23/EC concerning the performances of analytical methods and the interpretation of results. Off. J. Eur. Union 2002, L221, 8–36.
[29]
Knecht, J.; Stork, G. Percentage and logarithmic procedures for calculation of calibration curves, Fresen. Z. Anal. Chem. 1974, 270, 97–99, doi:10.1007/BF00434058.
[30]
Heitzman, R.J. Veterinary Drug Residues; Report Eur. 14126-EN; Commision of the EC: Brussels, Belgium and Luxembourg, Luxembourg, 1994.
[31]
Studies to Evaluate the Metabolism and Residue Kinetics of Veterinary Drugs in Food Producing Animals: Validation of Analytical Methods Used in Residue Depletion Studies; VICH GL 49 (2012-Final); U.S. Department of Health and Human Services Food and Drug Administration Center for Veterinary Medicine: Silver Spring, MD, USA, 2011.
[32]
European Commission. Commission Regulation No 429/2008 of 25 April 2008 on Detailed Rules for the Implementation of Regulation (EC) No 1831/2003 of the European Parliament and of the Council as Regards the Preparation and the Presentation of Applications and the Assessment and the Authorisation of Feed Additives. Off. J. Eur. Union 2008, L133, 1–65.
[33]
Eriksen, G.S.; Pettersson, H. Toxicological evaluation of trichothecenes in animal feed. Anim. Feed Sci. Technol. 2004, 114, 205–239, doi:10.1016/j.anifeedsci.2003.08.008.
[34]
Riond, J.L.; Riviere, J.E. Pharmacokinetics and metabolic inertness of doxycycline in young pigs. Am. J. Vet. Res. 1990, 51, 1271–1275. 2386327
[35]
Berthon, G.; Brion, M.; Lambs, L. Metal ion-tetracycline interactions in biological fluids. 2. Potentiometric study of magnesium complexes with tetracycline, oxytetracycline, doxycycline, and minocycline, and discussion of their possible influence on the bioavailability of these antibiotics in blood plasma. J. Inorg. Biochem. 1983, 19, 1–18, doi:10.1016/0162-0134(83)85009-0.
[36]
Arias, M.; Garcia-Falcon, M.S.; Garcia-Rio, L.; Mejuto, J.C.; Rial-Otero, R.; Simal-Gandara, J. Binding constants of oxytetracycline to animal feed divalent cations. J. Food Eng. 2007, 78, 69–73, doi:10.1016/j.jfoodeng.2005.09.016.
