Effects of BCRP and P-gp Modulators on the Penetration of Aflatoxin B-1 into the Mouse Brain


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Tras B., Cetin G., Uney K., Dik B., Corum O., ATALAY S.

KAFKAS UNIVERSITESI VETERINER FAKULTESI DERGISI, cilt.23, sa.1, ss.95-100, 2017 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 23 Sayı: 1
  • Basım Tarihi: 2017
  • Doi Numarası: 10.9775/kvfd.2016.15904
  • Dergi Adı: KAFKAS UNIVERSITESI VETERINER FAKULTESI DERGISI
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, TR DİZİN (ULAKBİM)
  • Sayfa Sayıları: ss.95-100
  • Erzincan Binali Yıldırım Üniversitesi Adresli: Evet

Özet

This study was conducted to determine whether the plasma and brain concentrations of AFB(1) 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 AFB(1) 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 AFB(1), blood and brain samples were collected from the animals in Groups 2 to 5. AFB(1) concentrations were determined using an HPLC system with fluorescence detection. Individual and simultaneous administration of prazosin and zosuquidar significantly reduced the brain concentrations of AFB(1) in comparison to a single administration of AFB(1) (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 AFB(1) poisoning.