期刊
BIOLOGICAL & PHARMACEUTICAL BULLETIN
卷 29, 期 12, 页码 2359-2361出版社
PHARMACEUTICAL SOC JAPAN
DOI: 10.1248/bpb.29.2359
关键词
ochnaflavone; biflavonoid; secretory phospholipase A(2); CCl4; rat liver microsome; lipid peroxidation
This study investigated the protective effects of a group IIA secretory phospholipase A(2) (sPLA(2)-IIA) inhibitor, ochnaflavone, on the progression of carbon tetrachloride (CCl4)-induced acute liver injury in rat liver microsomes in vitro. When rat liver was incubated at 37 degrees C in the presence of CCl4, the level of phosphatidylethanolamine (PE) degradation increased markedly compared with the control. The rat 14 kDa platelet PLA(2) antibody, R377, suppressed the degradation of PE. Pretreating the microsome with ochnaflavone (2-16 mu M) reduced the level of PE degradation in a dose dependent manner. In addition, p-bromophenacy bromide (p-BPB), which is a PLA(2) inhibitor, also inhibited PE degradation. However, the inhibitory activity was weaker than that of ochnaflavone. Further investigation showed that ochnaflavone not only inhibited the purified rat platelet sPLA(2) activity in a dose dependent manner with an IC50 value of 3.45 mu M, when arachidonyl PE was used as a substrate, but also inhibited lipid peroxidation in a dose dependent manner with an IC50 value of 7.16 mu M. This result suggests that ochnaflavone prevents the progression of CCl4-induced PE hydrolysis by inhibiting the endogenous sPLA 2 activity.
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