Gene expression kinetics of renal transporters induced by ochratoxin A in male and female F344 rats. (December 2016)

• Record Type: Journal Article
• Authors: Pastor, Laura; Vettorazzi, Ariane; Campión, Javier; Cordero, Paul; López de Cerain, Adela
• Is Part Of: Food and chemical toxicology. Volume 98:Part B(2016)
• Page Start: 169
• Page End: 178
• Publication Date: 2016-12
• Subjects: Ochratoxin A (OTA) -- Sex -- Kidney transporters -- Gene expression -- F344 rat -- Reference gene; 18S 18S ribosomal RNA -- Abc ATP-binding cassette -- Actb actin beta -- Bcrp breast cancer resistance protein -- bw body weight -- cDNA complementary DNA (deoxyribonucleic acid) -- Cmax maximum concentration -- Ct threshold cycle -- CV coefficient of variation -- EFSA European Food Safety Authority -- F female -- F344 Fisher 344 -- Gapdh glyceraldehyde-3-phosphate dehydrogenase -- IARC International Agency for Research on Cancer -- M male -- mRNA messenger RNA (ribonucleic acid) -- MIQE Minimum Information for Publication of Quantitative Real-Time PCR Experiments -- MoA mechanism of action -- Mrp multidrug resistance protein -- NaHCO3 sodium hydrogen carbonate -- NTP National Toxicology Program -- Oat organic anion transporter -- Oatp organic anion transporter polypeptide -- OTA ochratoxin A -- qPCR quantitative polymerase chain reaction -- Pept oligopeptide transporter -- Ppia peptidylprolyl isomerase A (cyclophilin A) -- Q relative quantification level -- RT reverse transcription -- RT-qPCR reverse transcription quantitative real-time polymerase chain reaction -- SD standard deviation -- Slc solute carrier -- SV stability value -- Taq Thermus aquaticus -- Ubc ubiquitin C -- WHO World Health Organization; Toxicology -- Periodicals; Food poisoning -- Periodicals; Food Poisoning -- Periodicals; Toxicology -- Periodicals; Toxicologie -- Périodiques; Intoxications alimentaires -- Périodiques; Food poisoning; Toxicology; Periodicals; Electronic journals; 615.9
• DOI: 10.1016/j.fct.2016.10.019
• Languages: English
• ISSNs: 0278-6915

Abstract

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. Highlights: Sex-biased basal expression of Oat2 (F > M), Bcrp and Oatp1 (M > F) was confirmed. Single ochratoxin A dose had a sex- and time-dependent effect in some transporters. A low ochratoxin A dose induced Oat2 in males. A low ochratoxin A dose decreased Oat 2 in females. Oat2 induced expression might explain a male specific early response to ochratoxin A.