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In vitro quantitative determination of the concentration of the polymerization agent methyl 2-benzoylbenzoate in intravenous injection solution and the cytotoxic effects of the chemical on normal human peripheral blood mononuclear cells

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Abstract

In previous studies, we detected the photoinitiators 1-hydroxycyclohexyl phenyl ketone (1-HCHPK) and 2-methyl-4'-(methylthio)-2-morpholinopropiophenone (MTMP) in an intravenous injection solution. Importantly, 1-HCHPK and MTMP have been demonstrated to be cytotoxic to normal human peripheral blood (PB) mononuclear cells (MNC). Cell death (apoptosis) pathways can be classified into two modes, caspase-dependent and -independent pathways. However, it is unclear whether methyl 2-benzoylbenzoate (MBB) induces the caspase-dependent and/or -independent pathway in normal human PBMNC. In the present in vitro study, we examined the levels of MBB in a solution from an intravenous fluid bag and the cytotoxicity of MBB towards normal human PBMNC via the caspase-8-, caspase-9-, or apoptosis-inducing factor (AIF)-mediated apoptosis pathways. We found that extracts from the injection solution had been contaminated with approximately 80 μM of the photoinitiator MBB. In addition, MBB induced apoptosis in the high concentration range in normal human PBMNC in vitro. Moreover, we found that MBB-induced apoptosis occurs via the caspase-9 pathway, but not the AIF pathway. In conclusion, we suggest that MBB has cytotoxic effects on normal human PBMNC in vitro, which are mediated via the caspase-dependent pathway.

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Authors and Affiliations

  1. Department of Clinical Pharmacy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1, Shikata-cho, Kita-ku, Okayama, 700-8558, Japan

    Chiaki Tsuboi, Kenta Yagi, Taro Miura, Yoshihisa Kitamura & Toshiaki Sendo

  2. Department of Pharmacy, Okayama University Hospital, 2-5-1, Shikata-cho, Kita-ku, Okayama, 700-8558, Japan

    Yoichi Kawasaki, Satoru Esumi, Yoshihisa Kitamura & Toshiaki Sendo

  3. Department of Hygiene, Kawasaki Medical School, 577 Matsushima, Kurashiki, 701-0192, Japan

    Kei Yoshitome

  4. Department of Brain Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1, Shikata-cho, Kita-ku, Okayama, 700-8558, Japan

    Ikuko Miyazaki & Masato Asanuma

Authors
  1. Chiaki Tsuboi
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  2. Yoichi Kawasaki
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  3. Kei Yoshitome
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  4. Kenta Yagi
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  5. Taro Miura
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  6. Satoru Esumi
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  7. Ikuko Miyazaki
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  8. Masato Asanuma
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  9. Yoshihisa Kitamura
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  10. Toshiaki Sendo
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Correspondence to Yoshihisa Kitamura.

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Responsible editor: Philippe Garrigues

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Tsuboi, C., Kawasaki, Y., Yoshitome, K. et al. In vitro quantitative determination of the concentration of the polymerization agent methyl 2-benzoylbenzoate in intravenous injection solution and the cytotoxic effects of the chemical on normal human peripheral blood mononuclear cells. Environ Sci Pollut Res 23, 10262–10269 (2016). https://doi.org/10.1007/s11356-016-6332-y

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  • DOI: https://doi.org/10.1007/s11356-016-6332-y

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