Kidney and liver distribution of ochratoxin A in male and female F344 rats

• Published in: Food and chemical toxicology 2011-09, Vol.49 (9), p.1935-1942
• Main Authors: Vettorazzi, Ariane, de Trocóniz, Iñaki Fernández, González-Peñas, Elena, Arbillaga, Leire, Corcuera, Laura-Ana, Gil, Ana Gloria, de Cerain, Adela López
• Format: Article
• Language: English
• Subjects: adults; Animals; bioavailability; Biological and medical sciences; Body weight; Compartments; Female; gender differences; Kidney; Kidney - metabolism; Kidneys; Liver; Liver - metabolism; Male; Male and female F344 rat; Males; Medical sciences; Ochratoxin A; Ochratoxins - pharmacokinetics; Organs; Plant poisons toxicology; Population kinetic analysis; Rats; Rats, Inbred F344; Sex; Tissue Distribution; Toxicology
• ISSN: 0278-6915; 1873-6351
• DOI: 10.1016/j.fct.2011.04.021

► OTA levels in kidney and liver after one or repeated oral doses to F344 rats both sexes. ► Concentrations very similar between both organs. ► Distribution from the central compartment, and elimination from the liver compartment. ► Sex differences observed in organs due to differences in bioavailability. ► The apparent volume of distribution of organs increased significantly with body weight. The impact of age and gender on Ochratoxin A (OTA) distribution in kidney and liver were studied. OTA was quantified in kidney and liver of young and mature rats of both sexes. Data was fit simultaneously using the population approach with NONMEM program. Fed and fasted mature males showed a 30% decrease and an 11% increase in relative bioavailability, respectively, in comparison with the rest of the groups. The OTA concentrations reached in kidney and liver were very similar between both organs. The models that best fit to data were the ones that considered that distribution of OTA to kidney and liver occurs from the central compartment and that elimination occurs mainly from the liver compartment. The kinetic analysis revealed that both, the apparent volume of distribution of the central compartment (V/F) and the apparent volume of distribution of the liver and kidney compartments (VL,K/F) increased significantly with body weight. Thus, the sex differences observed in organs distribution are a reflection of the differences in relative bioavailability observed in adult males, as a consequence of the fed and fasted conditions and to the significant higher body weight of mature males which directly affected the V/F and VL,K/F.