Kafkas Üniversitesi Veteriner Fakültesi Dergisi 2017 , Vol 23 , Issue 1
Effects of BCRP and P-gp Modulators on the Penetration of Aflatoxin B1 into the Mouse Brain
1Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, University of Selcuk, TR-42031 Konya - TURKEY
2Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, University of Mehmet Akif Ersoy, TR-15030 Burdur - TURKEY
3Deptartment of Pharmacology and Toxicology, Faculty of Veterinary Med., University of Dicle, TR-21280 Diyarbakır - TURKEY
4Konya Laboratory and Warehousing, Agricultural, Food, Energy Inc.,TR-42050 Konya - TURKEY
DOI : 10.9775/kvfd.2016.15904 This study was conducted to determine whether the plasma and brain concentrations of AFB1 are affected by the modulation of P-gp and BCRP using zosuquidar (ZQR) and prazosin (PRZ), respectively. In this study, a total of 40 healthy adult male BALB/c mice (32±3.7 g) were used. The animals were randomly divided into 5 groups, with 8 animals per group. Group 1 was used for method validation. Group 2 (AF) received intraperitoneal AFB1 at a dose of 20 mg/kg of body weight. Groups 3 (AF+PRZ), 4 (AF+ZQR), and 5 (AF+PRZ+ZQR) received 20 mg/kg of AFB1 intraperitoneally 30 min after the intraperitoneal administration of prazosin (0.3 mg/kg), zosuquidar (25 mg/kg), and prazosin+zosuquidar (0.3 mg/kg prazosin + 25 mg/kg zosuquidar), respectively. Six hours after the administration of AFB1, blood and brain samples were collected from the animals in Groups 2 to 5. AFB1 concentrations were determined using an HPLC system with fluorescence detection. Individual and simultaneous administration of prazosin and zosuquidar significantly reduced the brain concentrations of AFB1 in comparison to a single administration of AFB1 (P<0.05). The brain/plasma ratio of the AF group was higher than that of the other groups (AF+PRZ, AF+ZQR, and AF+PRZ+ZQR) (P<0.05). Inducers of transmembrane proteins, especially BCRP, can be life saving during acute AFB1 poisoning. Keywords : Aflatoxin B1, Brain, Drug transporter proteins, Modulation, Mice