Abstract
Lipopolysaccharide (LPS), or bacterial endotoxin, is an important virulence factor in several human and animal pathologies. Oxazoline of Palmitoylethanolamide (PEAOXA) has shown strong anti-inflammatory activity in several animal models. LPS was applied for 24 h to zebrafish embryos to induce inflammation, and then the anti-inflammatory action of PEAOXA was evaluated for the first time in the zebrafish model (Danio rerio). Different concentrations of PEAOXA were tested for toxicity on zebrafish embryonic development; only the highest concentration of 30 mg/L showed toxic effects. Quantitative RT-PCR was applied to detect Tumor necrosis factor-α, Interleukin 1β, 6, and 8, and members of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB). Exposure to LPS induced an increase in pro-inflammatory cytokines (tumor necrosis factor and interleukin 1, 6, and 8) in both gene and protein expression, as well as an increase of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) and the nuclear factor kappa light polypeptide enhancer in B-cells inhibitor (IκBα) gene expression. Furthermore, acute LPS exposure also induced an increase in tryptase release, related to mast cell activity, and in the production of apoptosis-related proteins (caspase 3, bax, and bcl-2). Treatment with PEAOXA 10 mg/L significantly counteracts LPS-induced inflammation in terms of cytokine expression and decreases tryptase release and the apoptosis pathway.
Highlights
Inflammation can be defined as a natural bodily response that is triggered by an injurious stimulus or toxic condition
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We used zebrafish embryo and larva (Danio rerio) as a fish model to study the impact of LPS on fish inflammatory pathway and apoptosis and the protective role of Palmitoylethanolamide oxazoline (PEAOXA)
Summary
Inflammation can be defined as a natural bodily response that is triggered by an injurious stimulus or toxic condition. Several cytokines are involved in the inflammatory process, such as tumor necrosis factor (TNF) and interleukin (IL), which are secreted and released once damage occurs, and immune cells, such as macrophages, are activated [2,3,4]. The study in the early life stages of zebrafish allows the assessment of the innate defense mechanism without the involvement of adaptive immunity [5]. Lipopolysaccharide (LPS) normally bind toll-like receptor 4 (TLR4) on the surface of the cell membrane that leads to the activation of TIR-domain-containing adapter-inducing interferon-β (TRIF) signaling pathway or myeloid differentiation factor 88 (MyD88) [6,7]. As a consequence of NF-κB pathway activation, pro-inflammatory factors release occurs, such as IL-1β, IL-6, TNF-α [10]. Direct inhibition of cytokines or their release is considered a good anti-inflammatory strategy [10,11]
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