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Article

Rapid deconjugation of SN‑38 glucuronide and adsorption of released free SN‑38 by intestinal microorganisms in rat

  • Authors:
    • Akira Takakura
    • Akinobu Kurita
    • Takashi Asahara
    • Masanori Yokoba
    • Michiko Yamamoto
    • Shinichiro Ryuge
    • Satoshi Igawa
    • Yukitoshi Yasuzawa
    • Jiichiro Sasaki
    • Hirosuke Kobayashi
    • Noriyuki Masuda
  • View Affiliations / Copyright

    Affiliations: Department of Respiratory Medicine, Kitasato University School of Medicine, Sagamihara, Kanagawa 252-0374, Japan, Yakult Central Institute for Microbial Research, Kunitachi, Tokyo 186-8650, Japan, Department of Respiratory Medicine, Kitasato University School of Allied Health Sciences, Sagamihara, Kanagawa 252-0373, Japan
  • Pages: 520-524
    |
    Published online on: December 9, 2011
       https://doi.org/10.3892/ol.2011.519
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Abstract

One of the dose‑limiting toxicities of irinotecan hydrochloride (CPT‑11) is delayed‑onset diarrhea. CPT‑11 is converted to its active metabolite, SN‑38, which is conjugated to SN‑38 glucuronide (SN‑38G). SN‑38G excreted in the intestinal lumen is extensively deconjugated by bacterial β‑glucuronidase, resulting in the regeneration of SN‑38, which causes diarrhea. However, the deconjugation of SN‑38G by the intestinal microflora remains to be clarified. This study aimed to investigate the microbial transformation of SN‑38G by an anaerobic mixed culture of rat cecal microorganisms. Concentrations of SN-38G and SN-38 were then determined using high-performance liquid chromatography. Complete deconjugation of SN‑38G to SN‑38 in the mixed cultures was observed within 1 h of incubation, with 62.7% of the added SN‑38G being found in the supernatant. Approximately 80.4% of the SN‑38 in the supernatant was bound to protein, and the remaining 19.6% was detected as active free SN‑38. In total, only 12.3% (19.6 x 62.7%) of the SN‑38G added to the test tube was found in the supernatant in the ultrafiltrable free form, indicating that approximately 90% of the SN‑38G added to the growth medium either remained adsorbed onto the pelleted fraction or occurred in a protein‑bound form in the supernatant. The remaining 10% of the SN‑38G added to the growth medium existed in the unbound form, the form capable of causing damage to the intestinal membrane. In conclusion, these results indicated that the greater part of the SN‑38 produced from SN‑38G by the action of bacterial β‑glucuronidase is rapidly adsorbed onto intestinal bacterial cell walls or dietary fibers in pelleted fraction, and only 10% remains in the ultrafiltrable unbound form in the intestinal luminal fluid.
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Copy and paste a formatted citation
Spandidos Publications style
Takakura A, Kurita A, Asahara T, Yokoba M, Yamamoto M, Ryuge S, Igawa S, Yasuzawa Y, Sasaki J, Kobayashi H, Kobayashi H, et al: Rapid deconjugation of SN‑38 glucuronide and adsorption of released free SN‑38 by intestinal microorganisms in rat. Oncol Lett 3: 520-524, 2012.
APA
Takakura, A., Kurita, A., Asahara, T., Yokoba, M., Yamamoto, M., Ryuge, S. ... Masuda, N. (2012). Rapid deconjugation of SN‑38 glucuronide and adsorption of released free SN‑38 by intestinal microorganisms in rat. Oncology Letters, 3, 520-524. https://doi.org/10.3892/ol.2011.519
MLA
Takakura, A., Kurita, A., Asahara, T., Yokoba, M., Yamamoto, M., Ryuge, S., Igawa, S., Yasuzawa, Y., Sasaki, J., Kobayashi, H., Masuda, N."Rapid deconjugation of SN‑38 glucuronide and adsorption of released free SN‑38 by intestinal microorganisms in rat". Oncology Letters 3.3 (2012): 520-524.
Chicago
Takakura, A., Kurita, A., Asahara, T., Yokoba, M., Yamamoto, M., Ryuge, S., Igawa, S., Yasuzawa, Y., Sasaki, J., Kobayashi, H., Masuda, N."Rapid deconjugation of SN‑38 glucuronide and adsorption of released free SN‑38 by intestinal microorganisms in rat". Oncology Letters 3, no. 3 (2012): 520-524. https://doi.org/10.3892/ol.2011.519
Copy and paste a formatted citation
x
Spandidos Publications style
Takakura A, Kurita A, Asahara T, Yokoba M, Yamamoto M, Ryuge S, Igawa S, Yasuzawa Y, Sasaki J, Kobayashi H, Kobayashi H, et al: Rapid deconjugation of SN‑38 glucuronide and adsorption of released free SN‑38 by intestinal microorganisms in rat. Oncol Lett 3: 520-524, 2012.
APA
Takakura, A., Kurita, A., Asahara, T., Yokoba, M., Yamamoto, M., Ryuge, S. ... Masuda, N. (2012). Rapid deconjugation of SN‑38 glucuronide and adsorption of released free SN‑38 by intestinal microorganisms in rat. Oncology Letters, 3, 520-524. https://doi.org/10.3892/ol.2011.519
MLA
Takakura, A., Kurita, A., Asahara, T., Yokoba, M., Yamamoto, M., Ryuge, S., Igawa, S., Yasuzawa, Y., Sasaki, J., Kobayashi, H., Masuda, N."Rapid deconjugation of SN‑38 glucuronide and adsorption of released free SN‑38 by intestinal microorganisms in rat". Oncology Letters 3.3 (2012): 520-524.
Chicago
Takakura, A., Kurita, A., Asahara, T., Yokoba, M., Yamamoto, M., Ryuge, S., Igawa, S., Yasuzawa, Y., Sasaki, J., Kobayashi, H., Masuda, N."Rapid deconjugation of SN‑38 glucuronide and adsorption of released free SN‑38 by intestinal microorganisms in rat". Oncology Letters 3, no. 3 (2012): 520-524. https://doi.org/10.3892/ol.2011.519
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