کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5558335 | 1561133 | 2017 | 8 صفحه PDF | دانلود رایگان |

Highlight
- Mouse Bcrp can mediate apically directed transport of OTA at pHÂ 7.4.
- Both mBcrp and hBCRP can transport OTA at pHÂ 6.4.
- There was modest transport of OTA by mMrp2 and hMRP2 at pHÂ 6.4, but not pHÂ 7.4.
- OATP1A2 and OATP2B1 mediated uptake of OTA both at pHÂ 7.4 and 6.4.
- OATP1B1 mediated uptake of OTA only at pHÂ 7.4.
Ochratoxin A (OTA) is a fungal secondary metabolite that can contaminate various foods. OTA has several toxic effects like nephrotoxicity, hepatotoxicity, and neurotoxicity in different animal species, but its mechanisms of toxicity are still unclear. How OTA accumulates in kidney, liver, and brain is as yet unknown, but transmembrane transport proteins are likely involved. We studied transport of OTA in vitro, using polarized MDCKII cells transduced with cDNAs of the efflux transporters mouse (m)Bcrp, human (h)BCRP, mMrp2, or hMRP2, and HEK293 cells overexpressing cDNAs of the human uptake transporters OATP1A2, OATP1B1, OATP1B3, or OATP2B1 at pHÂ 7.4 and 6.4. MDCKII-mBcrp cells were more resistant to OTA toxicity than MDCKII parental and hBCRP-transduced cells. Transepithelial transport experiments showed some apically directed transport by MDCKII-mBcrp cells at pHÂ 7.4, whereas both mBcrp and hBCRP clearly transported OTA at pHÂ 6.4. There was modest transport of OTA by mMrp2 and hMRP2 only at pHÂ 6.4. OATP1A2 and OATP2B1 mediated uptake of OTA both at pHÂ 7.4 and 6.4, but OATP1B1 only at pHÂ 7.4. There was no detectable transport of OTA by OATP1B3. Our data indicate that human BCRP and MRP2 can mediate elimination of OTA from cells, thus reducing OTA toxicity. On the other hand, human OATP1A2, OATP1B1, and OATP2B1 can mediate cellular uptake of OTA, which could aggravate OTA toxicity.
Journal: Toxicology and Applied Pharmacology - Volume 329, 15 August 2017, Pages 18-25