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
TRAS B1, CETIN G2, UNEY K1, DIK B1, CORUM O3, ATALAY S4
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