The In Vitro and In Vivo Effect of Lipoxygenase Pathway Inhibitors Nordihydroguaiaretic Acid and Its Derivative Tetra- O -methyl Nordihydroguaiaretic Acid against Brucella abortus 544open accessThe In Vitro and In Vivo Effect of Lipoxygenase Pathway Inhibitors Nordihydroguaiaretic Acid and Its Derivative Tetra-O-methyl Nordihydroguaiaretic Acid against Brucella abortus 544
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- The In Vitro and In Vivo Effect of Lipoxygenase Pathway Inhibitors Nordihydroguaiaretic Acid and Its Derivative Tetra-O-methyl Nordihydroguaiaretic Acid against Brucella abortus 544
- Reyes Alisha Wehdnesday Bernardo; Kim Heejin; Huy Tran Xuan Ngoc; Nguyen Trang Thi; Min Wongi; Lee Dongho; Hur Jin; Lee John Hwa; 김석
- Issue Date
- 5-Lipoxygenase; Brucella abortus; leukotriene B4; thromboxane A2; splenic proliferation
- Journal of Microbiology and Biotechnology, v.32, no.9, pp.1126 - 1133
- Journal Title
- Journal of Microbiology and Biotechnology
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- End Page
- This study investigated the contribution of lipoxygenase (LOX) inhibitors, nordihydroguaiaretic acid (NDGA), tetra-O-methyl nordihydroguaiaretic acid (M4N) and zileuton (ZIL), and thromboxane A2 (TXA2) inhibitor 4,5-diphenylimidazole (DPI) in the proliferation of Brucella abortus infection. None of the compounds affected the uptake of Brucella into the macrophages. We determined the effect of neutralizing leukotriene B4 (LTB4) receptor and showed that the uptake of the bacteria was inhibited at 30 min post-infection. M4N treatment attenuated intracellular survival of Brucella at 2 h post-incubation but it was not observed in the succeeding time points. DPI treatment showed reduced survival of Brucella at 24 h post-incubation while blocking LTB4 receptor was observed to have a lower intracellular growth at 48 h post-incubation suggesting different action of the inhibitors in the course of the survival of Brucella within the cells. Reduced proliferation of the bacteria in the spleens of mice was observed in animals treated with ZIL or DPI. Increased serum cytokine level of TNF-α and MCP-1 was observed in mice treated with M4N or ZIL while a lower IFN-γ level in ZIL-treated mice and a higher IL-12 serum level in DPI-treated mice were observed at 7 d postinfection.
At 14 d post-infection, ZIL-treated mice displayed reduced serum level of IL-12 and IL-10.
Overall, inhibition of 5-LOX or TXA2 or a combination therapy promises a potential alternative therapy against B. abortus infection. Furthermore, strong ligands for LTB4 receptor could also be a good candidate for the control of Brucella infection.
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- 수의과대학 > Department of Veterinary Medicine > Journal Articles
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