| First Author | Furukawa K | Year | 2024 |
| Journal | Environ Health Prev Med | Volume | 29 |
| Pages | 21 | PubMed ID | 38522903 |
| Mgi Jnum | J:357391 | Mgi Id | MGI:7705427 |
| Doi | 10.1265/ehpm.23-00284 | Citation | Furukawa K, et al. (2024) Role of ABCB1 and ABCB4 in renal and biliary excretion of perfluorooctanoic acid in mice. Environ Health Prev Med 29:21 |
| abstractText | BACKGROUND: Perfluorooctanoic acid (PFOA) is one of the major per- and polyfluoroalkyl substances. The role of ATP-binding cassette (ABC) transporters in PFOA toxicokinetics is unknown. METHODS: In this study, two ABC transporters, ABCB1 and ABCB4, were examined in mice with single intravenous PFOA administration (3.13 micromol/kg). To identify candidate renal PFOA transporters, we used a microarray approach to evaluate changes in gene expression of various kidney transporters in Abcb4 null mice. RESULTS: Biliary PFOA concentrations were lower in Abcb4 null mice (mean +/- standard deviation: 0.25 +/- 0.12 microg/mL) than in wild-type mice (0.87 +/- 0.02 microg/mL). Immunohistochemically, ABCB4 expression was confirmed at the apical region of hepatocytes. However, renal clearance of PFOA was higher in Abcb4 null mice than in wild-type mice. Among 642 solute carrier and ABC transporters, 5 transporters showed significant differences in expression between wild-type and Abcb4 null mice. These candidates included two major xenobiotic transporters, multidrug resistance 1 (Abcb1) and organic anion transporter 3 (Slc22a8). Abcb1 mRNA levels were higher in Abcb4 null mice than in wild-type mice in kidney. In Abcb4 null mice, Abcb1b expression was enhanced in proximal tubules immunohistochemically, while that of Slc22a8 was not. Finally, in Abcb1a/b null mice, there was a significant decrease in the renal clearance of PFOA (0.69 +/- 0.21 vs 1.1 mL +/- 0.37/72 h in wild-type mice). A homology search of ABCB1 showed that several amino acids are mutated in humans compared with those in rodents and monkeys. CONCLUSIONS: These findings suggest that, in the mouse, Abcb4 and Abcb1 are excretory transporters of PFOA into bile and urine, respectively. |
