Effects of fasting and gender on ochratoxin A toxicokinetics in F344 rats

被引:17
作者
Vettorazzi, A. [1 ]
Troconiz, I. F. [2 ]
Gonzalez-Penas, E. [3 ]
Corcuera, L. A. [1 ]
Arbillaga, L. [1 ]
Gil, A. G. [1 ]
Nagy, J. M. [4 ]
Mantle, P. G. [5 ]
de Cerain, A. Lopez [1 ]
机构
[1] Univ Navarra, Fac Pharm, Dept Nutr & Food Sci Physiol & Toxicol, E-31008 Pamplona, Spain
[2] Univ Navarra, Fac Pharm, Dept Pharm & Pharmaceut Technol, E-31008 Pamplona, Spain
[3] Univ Navarra, Fac Pharm, Dept Organ & Pharmaceut Chem, E-31008 Pamplona, Spain
[4] Univ London Imperial Coll Sci Technol & Med, Inst Biomed Engn, London SW7 2AZ, England
[5] Univ London Imperial Coll Sci Technol & Med, Ctr Environm Policy, London SW7 2AZ, England
关键词
Ochratoxin A; Toxicokinetic; Bioavailability; Male and female F344 rat; Food; Alpha-2u-globulin; BINDING; PLASMA; PHARMACOKINETICS; NEPHROPATHY; TUMORS; SECRETION; TOXICITY; EFFICACY; ANIMALS; PROFILE;
D O I
10.1016/j.fct.2010.08.012
中图分类号
TS2 [食品工业];
学科分类号
0832 ;
摘要
Ochratoxin A (OTA) is a mycotoxin that causes renal tumors in rats, particularly in males. In previous kinetic studies performed in fed conditions (Vettorazzi et al., 2008), mature F344 male rats presented a significantly lower OTA bioavailability than females and young animals. The objective of the present study was to evaluate two factors which could explain this different kinetic profile: the presence of food and the male-specific protein alpha-2u-globulin. Therefore, a 24 h kinetic study has been performed in rats under fasting conditions. Food ingestion has been controlled in both sexes during two months. The presence of alpha-2u-globulin in the urine has been analyzed with SOS-gradient mini-gel electrophoresis. Fasting tends to increase the maximum OTA plasma concentrations and the rate of absorption. The relative bioavailability is significantly increased under fasting conditions only in males. Mature males consumed a higher amount of food but, as the OTA dose administered, it was proportional to body weight. The reason why the OTA bioavailability is more affected in presence of food only in males is unclear. Several possibilities, such as differences in gastric emptying, OTA-food interactions and the involvement of alpha-2u-globulin are discussed. (C) 2010 Elsevier Ltd. All rights reserved.
引用
收藏
页码:3159 / 3166
页数:8
相关论文
共 48 条
[31]   Ochratoxin A: An overview on toxicity and carcinogenicity in animals and humans [J].
Pfohl-Leszkowicz, Annie ;
Manderville, Richard A. .
MOLECULAR NUTRITION & FOOD RESEARCH, 2007, 51 (01) :61-99
[32]   The role of α2u-globulin in ochratoxin A induced renal toxicity and tumors in F344 rats [J].
Rásonyi, T ;
Schlatter, J ;
Dietrich, DR .
TOXICOLOGY LETTERS, 1999, 104 (1-2) :83-92
[33]   Toxicokinetics and toxicodynamics of ochratoxin A, an update [J].
Ringot, D ;
Chango, A ;
Schneider, YJ ;
Larondelle, Y .
CHEMICO-BIOLOGICAL INTERACTIONS, 2006, 159 (01) :18-46
[34]   INTERPRETATION OF MALE-RAT RENAL TUBULE TUMORS [J].
RODGERS, IS ;
BAETCKE, KP .
ENVIRONMENTAL HEALTH PERSPECTIVES, 1993, 101 :45-52
[35]   Acute neurotoxic effects of the fungal metabolite ochratoxin-A [J].
Sava, V ;
Reunova, O ;
Velasquez, A ;
Harbison, R ;
Sánchez-Ramos, J .
NEUROTOXICOLOGY, 2006, 27 (01) :82-92
[36]   Ochratoxin A secretion by ATP-dependent membrane transporters in Caco-2 cells [J].
Schrickx, J ;
Lektarau, Y ;
Fink-Gremmels, J .
ARCHIVES OF TOXICOLOGY, 2006, 80 (05) :243-249
[37]  
Shargel L., 2005, APPL BIOPHARMACEUTIC, V5th
[38]   Strain-specific mammary proliferative lesion development following lifetime oral administration of ochratoxin A in DA and lewis rats [J].
Son, WC ;
Kamino, K ;
Lee, YS ;
Kang, KS .
INTERNATIONAL JOURNAL OF CANCER, 2003, 105 (03) :305-311
[39]   Spontaneous mycotoxic nephropathy in Bulgarian chickens with unclarified mycotoxin aetiology [J].
Stoev, SD ;
Daskalov, H ;
Radic, B ;
Domijan, AM ;
Peraica, M .
VETERINARY RESEARCH, 2002, 33 (01) :83-93
[40]   PHARMACOKINETICS OF OCHRATOXIN-A IN RATS [J].
SUZUKI, S ;
SATOH, T ;
YAMAZAKI, M .
JAPANESE JOURNAL OF PHARMACOLOGY, 1977, 27 (05) :735-744