title: Gene expression kinetics of renal transporters induced by ochratoxin A in male and female F344 rats.
abstract: Ochratoxin A (OTA) is a mycotoxin that contaminates foodstuffs. The most relevant concern is its high kidney carcinogenicity in male rats and its unclear mechanism of action. It has been hypothesized that variations in transport mechanisms in kidney cells may be the reason of different sex-dependent sensitivities towards OTA. The aim of this study was to analyze, by RT- qPCR, renal transporters expression in 15-week-old male (M) and female (F) F344 rats at basal level and after single oral OTA administration (0.50 mg/kg bw). Temporal profiles (24h, 48h, 72h, 96h, 1 and 2 months) were studied per sex and transporter. The reference gene for all comparisons was Ppia. At basal level, sex differences were confirmed for Oatp1, Bcrp (M>F) and Oat2 (F>M). OTA tended to inhibit the expression of almost all transporters in both sexes, but clearly induced the expression of Oat2 in males. Regarding time profiles, the highest sex differences involved Oat (Slc22) transporters: Oat2, Oat3 and Oat5 expression showed a significant increase in males (24h) while Oat1, Oat2 and Oat5 level decreased in females (48h). Overall, basal sex differences in F344 rats and the specific sex-dependent response to OTA of Oat2 might contribute to high kidney damage in male rats.
authors: Department of Pharmacology and Toxicology, Faculty of Pharmacy and Nutrition, University of Navarra, C/ Irunlarrea 1, 31008 Pamplona, Spain. Electronic address: lpcastro@alumni.unav.es.
authors: Laura
authors: L
authors: Pastor
authors: Department of Pharmacology and Toxicology, Faculty of Pharmacy and Nutrition, University of Navarra, C/ Irunlarrea 1, 31008 Pamplona, Spain. Electronic address: avettora@unav.es.
authors: Ariane
authors: A
authors: Vettorazzi
authors: Department of Food Science and Physiology, Faculty of Pharmacy and Nutrition, University of Navarra, C/ Irunlarrea 1, 31008 Pamplona, Spain; Current address: Making Genetics SL, Plaza CEIN 5, 31110 Noain, Spain. Electronic address: jcampion@making-genetics.eu.
authors: Javier
authors: J
authors: Campión
authors: Department of Food Science and Physiology, Faculty of Pharmacy and Nutrition, University of Navarra, C/ Irunlarrea 1, 31008 Pamplona, Spain; Current address: Institute for Liver and Digestive Health, University College London, Rowland Hill Street, London NW3 2PF, United Kingdom. Electronic address: paul.sanchez@ucl.ac.uk.
authors: Paul
authors: P
authors: Cordero
authors: Department of Pharmacology and Toxicology, Faculty of Pharmacy and Nutrition, University of Navarra, C/ Irunlarrea 1, 31008 Pamplona, Spain. Electronic address: acerain@unav.es.
authors: Adela
authors: A
authors: López de Cerain
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2 / Q000235:genetics*; D000818:Animals; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007700:Kinetics; D008297:Male; D009183:Mycotoxins / Q000494:pharmacology*; D009793:Ochratoxins / Q000494:pharmacology*; D029362:Organic Anion Transporters, Sodium-Independent / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011916:Rats, Inbred F344; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012737:Sex Factors
chemical_list: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; C489249:Abcg2 protein, rat; D009183:Mycotoxins; D009793:Ochratoxins; D029362:Organic Anion Transporters, Sodium-Independent; D012333:RNA, Messenger; C088800:Slc22a7 protein, rat; C421102:Slco1a1 protein, rat; C025589:ochratoxin A
keywords: F344 rat; Gene expression; Kidney transporters; Ochratoxin A (OTA); Reference gene; Sex