Assessment of intestinal absorption/metabolism of 3-chloro-1,2-propanediol (3-MCPD) and three 3-MCPD monoesters by Caco-2 cells

被引:25
作者
Araujo, Magali [1 ]
Beekman, Jessica K. [2 ]
Mapa, Mapa S. T. [1 ]
MacMahon, Shaun [3 ]
Zhao, Yang [1 ]
Flynn, Thomas J. [1 ]
Flannery, Brenna [4 ]
Mossoba, Miriam E. [1 ]
Sprando, Robert L. [1 ]
机构
[1] US FDA, Ctr Food Safety & Appl Nutr, OARSA, Div Toxicol, 8301 Muirkirk Rd,MOD 1 R 1003, Laurel, MD 20708 USA
[2] US FDA, Ctr Food Safety & Appl Nutr, ORS, Div Analyt Chem, College Pk, MD 20740 USA
[3] US FDA, Ctr Food Safety & Appl Nutr, ORS, DBC, College Pk, MD 20740 USA
[4] US FDA, Ctr Food Safety & Appl Nutr, OAO, DRDA,Contaminant Assessment Branch, College Pk, MD 20740 USA
关键词
3-MCPD; 3-MCPD monoesters; Caco-2; cells; Intestinal absorption; FATTY-ACID ESTERS; RESOLUTION MASS-SPECTROMETRY; DRUG PERMEABILITY; 3-MONOCHLOROPROPANE-1,2-DIOL 3-MCPD; PROTEOMIC ANALYSIS; GLYCIDYL ESTERS; VEGETABLE-OILS; TOXICITY; METABOLISM; TRANSPORT;
D O I
10.1016/j.tiv.2020.104887
中图分类号
R99 [毒物学(毒理学)];
学科分类号
100405 ;
摘要
3-chloro-1,2-propanediol (3-MCPD) and 3-MCPD esters are contaminants present in a variety of processed foods, including infant formulas. Toxicological data are unavailable in humans, but rodent studies have demonstrated renal and testicular toxicity from 3-MCPD and 3-MCPD esters. There is evidence that 3-MCPD esters are hydrolyzed in the digestive system, releasing 3-MCPD that would be absorbed and induce damage. We assessed absorption and metabolism of 3-MCPD and three 3-MCPD monoesters, 1-oleoyl (1-Ol), 1-linoleoyl (1-Li) and 1-palmitoyl (1-Pa) commonly found in U.S. infant formula using differentiated Caco-2 cells. After 1-hour incubation, all three monoesters released free 3-MCPD and free fatty acids (FFA) into Caco-2 cell supernatants. Free 3-MCPD had a high apparent permeability (P-app = 30.36 +/- 1.31 cm/s x 10(-6)) suggesting that it is freely diffusible and highly absorbed by intestinal epithelium. 1-Li released 3-4-fold more 3-MCPD than 1-Ol and 1-Pa over 1 h, suggesting that this variable release rates might contribute to the overall in vivo exposure to 3-MCPD. None of the monoesters or FFA were detected in basolateral supernatants, suggesting that these compounds do not cross the intestinal wall without further transformation. In summary, this study provides relevant data to advance knowledge of in vivo intestinal absorption and metabolism of 3-MCPD monoesters.
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页数:6
相关论文
共 57 条
[1]   Relative oral bioavailability of 3-MCPD from 3-MCPD fatty acid esters in rats [J].
Abraham, Klaus ;
Appel, Klaus E. ;
Berger-Preiss, Edith ;
Apel, Elisabeth ;
Gerling, Susanne ;
Mielke, Hans ;
Creutzenberg, Otto ;
Lampen, Alfonso .
ARCHIVES OF TOXICOLOGY, 2013, 87 (04) :649-659
[2]  
[Anonymous], 2017, **DROPPED REF**
[3]   The Permeation of Acamprosate Is Predominantly Caused by Paracellular Diffusion across Caco-2 Cell Monolayers: A Paracellular Modeling Approach [J].
Antonescu, Irina E. ;
Rasmussen, Karina F. ;
Neuhoff, Sibylle ;
Frette, Xavier ;
Karlgren, Maria ;
Bergstrom, Christel A. S. ;
Nielsen, Carsten Uhd ;
Steffansen, Bente .
MOLECULAR PHARMACEUTICS, 2019, 16 (11) :4636-4650
[4]   Structure and function of extracellular phospholipase A1 belonging to the pancreatic lipase gene family [J].
Aoki, Junken ;
Inoue, Asuka ;
Makide, Kumiko ;
Saiki, Naoya ;
Arai, Hiroyuki .
BIOCHIMIE, 2007, 89 (02) :197-204
[5]   Caco-2 monolayers in experimental and theoretical predictions of drug transport (Reprinted from Advanced Drug Delivery Reviews, vol 22, pg 67-84, 1996) [J].
Artursson, P ;
Palm, K ;
Luthman, K .
ADVANCED DRUG DELIVERY REVIEWS, 2001, 46 (1-3) :27-43
[6]   A polymorphism in the human intestinal fatty acid binding protein alters fatty acid transport across Caco-2 cells [J].
Baier, LJ ;
Bogardus, C ;
Sacchettini, JC .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (18) :10892-10896
[7]   Toxicological assessment of 3-chloropropane-1,2-diol and glycidol fatty acid esters in food [J].
Bakhiya, Nadiya ;
Abraham, Klaus ;
Guertler, Rainer ;
Appel, Klaus Erich ;
Lampen, Alfonso .
MOLECULAR NUTRITION & FOOD RESEARCH, 2011, 55 (04) :509-521
[8]  
Barocelli E., 2011, EFSA Supporting Publications, V8
[9]   Absorption and metabolism of the food contaminant 3-chloro-1,2-propanediol (3-MCPD) and its fatty acid esters by human intestinal Caco-2 cells [J].
Buhrke, Thorsten ;
Weisshaar, Ruediger ;
Lampen, Alfonso .
ARCHIVES OF TOXICOLOGY, 2011, 85 (10) :1201-1208
[10]   Estimation of permeability by passive diffusion through Caco-2 cell monolayers using the drugs' lipophilicity and molecular weight [J].
Camenisch, G ;
Alsenz, J ;
van de Waterbeemd, H ;
Folkers, G .
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES, 1998, 6 (04) :313-319