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- W87288317 abstract "Neuroinflammation appears to involve release of thromboxane B2 (TXB2) and superoxide anion (O2−) by brain microglia (BMG). The purpose of this investigation was to determine the effect of five Hymeniacidon sp. amphilectane metabolites (HsH2.6, HsH1.11, HsH2.13, HsH2.29_456, and HsH2.11.X7.3) and two semi-synthetic analogs (HsH1.11x and HsH1.11X2) on TXB2 and O2− generation from E. coli LPS-activated rat BMG. Short and long term cell viability was assessed by lactate dehydrogenase (LDH) release (1.5 h) and mitochondrial dehydrogenase (MTH) activity (2.5–18 h), respectively. O2− levels were determined via superoxide dismutase-inhibitable reduction of ferricytochrome C and TXB2 by EIA. Results were the following (n=3–4): all Hymeniacidon sp. metabolites and analogs potently inhibited TXB2 (IC50=0.20–5.69 μM) with low LDH release and minimal MTH inhibition. Comparison of IC50 of closely related amphilectane diterpenes HsH2.13 (IC50~0.20 μM) and HsH1.11 (IC50~0.23 μM) supports the observation that bioactivity is associated with presence of two isonitrile groups. However, the amphilectane diterpenoid skeleton plays a significant role, as suggested by comparison between IC50 of these two compounds and HsH1.11X2 (IC50~3.14 μM), where original isonitriles have been replaced by formamide groups. Lack of O2− inhibition would appear to suggest that all Hymeniacidon sp. metabolites and derivatives inhibit TXB2 synthesis by a cyclooxygenase-dependent mechanism. Supported by Midwestern University and the RISE and SCORE Programs, University of Puerto Rico at the Río Piedras Campus." @default.
- W87288317 created "2016-06-24" @default.
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- W87288317 date "2010-04-01" @default.
- W87288317 modified "2023-10-03" @default.
- W87288317 title "Marine sponge Hymeniacidon sp. amphilectane metabolites potently inhibit rat brain microglia thromboxane B 2 generation" @default.
- W87288317 doi "https://doi.org/10.1096/fasebj.24.1_supplement.966.1" @default.
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