Effects of Decreased Vitamin D and Accumulated Uremic Toxin on Human CYP3A4 Activity in Patients with End-Stage Renal Disease
Abstract
:1. Introduction
2. Results
2.1. Effect of Uremic Serum or Uremic Toxins on Testosterone 6β-Hydroxylation in HLMs
2.2. CYP3A4 Activity in LS180 Cells Exposed to Uremic Serum or Uremic Toxins
2.3. Expression of CYP3A4, MDR1 and CYP24A1 mRNA in Uremic Serum-Treated LS180 Cells
2.4. Effects of 1,25-Dihydroxyvitamin D and Uremic Toxins on Induction of CYP3A4 mRNA Expression
3. Discussion
Uremic toxin | Serum concentration (μM) | Unbound fraction (%) | |
---|---|---|---|
Total | Unbound | ||
CMPF | 179.1 ± 6.9 | Not detected | Not calculation |
3-Indoxyl sulfate | 134.6 ± 0.7 | 20.2 ± 0.2 | 14 |
Indole-3-acetic acid | 9.2 ± 0.5 | 1.7 ± 0.04 | 18.5 |
Hippuric acid | 238.5 ± 2.1 | 131.4 ± 0.2 | 55.5 |
4. Materials and Methods
4.1. Materials
4.2. Sera
4.3. Analysis of Uremic Toxins in Uremic Serum
4.4. Detection of CYP3A4 Activity Using Testosterone 6β-Hydroxylation
4.5. Detection of CYP3A4 Activity in LS180 Cells by Using the P450-GloTM Assays Kit
4.6. Quantification of mRNA by Real-Time Reverse Transcription-Polymerase Chain Reaction Analysis
4.7. Quantification of 1,25-Dihydroxyvitamin D
4.8. Data Analysis
5. Conclusions
Acknowledgments
Conflicts of Interest
References
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Tsujimoto, M.; Nagano, Y.; Hosoda, S.; Shiraishi, A.; Miyoshi, A.; Hiraoka, S.; Furukubo, T.; Izumi, S.; Yamakawa, T.; Minegaki, T.; et al. Effects of Decreased Vitamin D and Accumulated Uremic Toxin on Human CYP3A4 Activity in Patients with End-Stage Renal Disease. Toxins 2013, 5, 1475-1485. https://doi.org/10.3390/toxins5081475
Tsujimoto M, Nagano Y, Hosoda S, Shiraishi A, Miyoshi A, Hiraoka S, Furukubo T, Izumi S, Yamakawa T, Minegaki T, et al. Effects of Decreased Vitamin D and Accumulated Uremic Toxin on Human CYP3A4 Activity in Patients with End-Stage Renal Disease. Toxins. 2013; 5(8):1475-1485. https://doi.org/10.3390/toxins5081475
Chicago/Turabian StyleTsujimoto, Masayuki, Yui Nagano, Satomi Hosoda, Asuka Shiraishi, Ayaka Miyoshi, Shima Hiraoka, Taku Furukubo, Satoshi Izumi, Tomoyuki Yamakawa, Tetsuya Minegaki, and et al. 2013. "Effects of Decreased Vitamin D and Accumulated Uremic Toxin on Human CYP3A4 Activity in Patients with End-Stage Renal Disease" Toxins 5, no. 8: 1475-1485. https://doi.org/10.3390/toxins5081475