1. Olaparib attenuates sepsis-induced acute multiple organ injury via ERK-mediated CD14 expression.
- Author
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Chen Z, Chen Y, Jin X, Liu Y, Shao Z, and Li Q
- Subjects
- Animals, Anti-Inflammatory Agents therapeutic use, Cytokines metabolism, Disease Models, Animal, Inflammation drug therapy, Inflammation Mediators metabolism, Lipopolysaccharide Receptors drug effects, Lung metabolism, Male, Mice, Lipopolysaccharide Receptors metabolism, Phthalazines pharmacology, Piperazines pharmacology, Sepsis drug therapy, Sepsis metabolism
- Abstract
Sepsis is characterized by persistent systemic inflammation, which can cause multi-organ dysfunction. The poly polymerase-1 inhibitor olaparib possesses anti-inflammatory properties. This study aimed to assess the effects of olaparib (pre- and post-treatments) on sepsis, and to investigate whether it could suppress CD14 expression via the ERK pathway in polymicrobial sepsis and peritoneal macrophages models. Sepsis was induced by cecal ligation and puncture in C57BL/6 male mice. Fifty mice were randomly divided into five groups: The sham group was treated with vehicle or olaparib, the cecal ligation and puncture group with vehicle or with olaparib (5 mg/kg i.p.) 1 h before or 2 h after surgery. Olaparib pretreatment significantly improved the survival of septic mice ( P < 0.001). Pre- and post-treatment of mice with olaparib partly alleviated cecal ligation and puncture-induced organ injury by decreasing the amounts of the pro-inflammatory mediators TNF-α and IL-6 as well as bacterial burden in the serum, peritoneal lavage fluid, and organs ( P < 0.05). The protective effect of olaparib was associated with CD14 suppression via inhibition of ERK activation. Olaparib facilitated negative regulation of ERK-mediated CD14 expression, which may contribute to multi-organ injury in sepsis.
- Published
- 2021
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