Tsuboi Chiaki, Kawasaki Yoichi, Yoshitome Kei, Yagi Kenta, Miura Taro, Esumi Satoru, Miyazaki Ikuko, Asanuma Masato, Kitamura Yoshihisa, Sendo Toshiaki
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.
Environ Sci Pollut Res Int. 2016 May;23(10):10262-9. doi: 10.1007/s11356-016-6332-y. Epub 2016 Apr 5.
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.
在先前的研究中,我们在一种静脉注射溶液中检测到了光引发剂1-羟基环己基苯基酮(1-HCHPK)和2-甲基-4'-(甲硫基)-2-吗啉代苯丙酮(MTMP)。重要的是,1-HCHPK和MTMP已被证明对正常人外周血(PB)单核细胞(MNC)具有细胞毒性。细胞死亡(凋亡)途径可分为两种模式,即半胱天冬酶依赖性和非依赖性途径。然而,尚不清楚2-苯甲酰苯甲酸甲酯(MBB)是否会在正常人外周血单核细胞中诱导半胱天冬酶依赖性和/或非依赖性途径。在本体外研究中,我们检测了静脉输液袋溶液中MBB的含量,以及MBB通过半胱天冬酶-8、半胱天冬酶-9或凋亡诱导因子(AIF)介导的凋亡途径对正常人外周血单核细胞的细胞毒性。我们发现注射溶液的提取物被大约80μM的光引发剂MBB污染。此外,MBB在体外高浓度范围内可诱导正常人外周血单核细胞凋亡。而且,我们发现MBB诱导的凋亡是通过半胱天冬酶-9途径发生的,而不是通过AIF途径。总之,我们认为MBB在体外对正常人外周血单核细胞具有细胞毒性作用,其通过半胱天冬酶依赖性途径介导。