title: 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.
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.
authors.affiliation: 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.
authors.forename: Chiaki
authors.initials: C
authors.lastname: Tsuboi
authors.affiliation: Department of Pharmacy, Okayama University Hospital, 2-5-1, Shikata-cho, Kita-ku, Okayama, 700-8558, Japan.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Kawasaki
authors.affiliation: Department of Hygiene, Kawasaki Medical School, 577 Matsushima, Kurashiki, 701-0192, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Yoshitome
authors.affiliation: 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.
authors.forename: Kenta
authors.initials: K
authors.lastname: Yagi
authors.affiliation: 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.
authors.forename: Taro
authors.initials: T
authors.lastname: Miura
authors.affiliation: Department of Pharmacy, Okayama University Hospital, 2-5-1, Shikata-cho, Kita-ku, Okayama, 700-8558, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Esumi
authors.affiliation: 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.
authors.forename: Ikuko
authors.initials: I
authors.lastname: Miyazaki
authors.affiliation: 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.
authors.forename: Masato
authors.initials: M
authors.lastname: Asanuma
authors.affiliation: 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. kitamu-y@cc.okayama-u.ac.jp.|Department of Pharmacy, Okayama University Hospital, 2-5-1, Shikata-cho, Kita-ku, Okayama, 700-8558, Japan. kitamu-y@cc.okayama-u.ac.jp.
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Kitamura
authors.affiliation: 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.|Department of Pharmacy, Okayama University Hospital, 2-5-1, Shikata-cho, Kita-ku, Okayama, 700-8558, Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Sendo
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D051033:Apoptosis Inducing Factor; D001565:Benzoates / Q000633:toxicity*; D020169:Caspases / Q000378:metabolism; D002478:Cells, Cultured; D006801:Humans; D007275:Injections, Intravenous; D007963:Leukocytes, Mononuclear / Q000187:drug effects*; D008928:Mitochondria / Q000378:metabolism; D058105:Polymerization; D012996:Solutions / Q000008:administration & dosage / Q000737:chemistry
chemical_list: D051033:Apoptosis Inducing Factor; D001565:Benzoates; D012996:Solutions; C000616131:methyl 2-benzoylbenzoate; D020169:Caspases
keywords: Apoptosis; Apoptosis-inducing factor; Caspase-9; Injection; Methyl 2-benzoylbenzoate; Photoinitiator