Dantas Kassyo L S, Bianchini Beatriz H S, da Silva Matheus D V, Piva Maiara, da Cunha Joice M, Zanoveli Janaina M, Cardoso Fernanda C, Vicentini Fabiana T M C, Ferraz Camila R, Clissa Patricia B, Casagrande Rubia, Verri Waldiceu A
Laboratory of Pain, Inflammation, Neuropathy, and Cancer, Department of Immunology, Parasitology and General Pathology, Londrina State University, Londrina 86057-970, PR, Brazil.
Department of Pharmacology, Federal University of Paraná, Curitiba 81531-980, PR, Brazil.
Toxins (Basel). 2025 Jul 25;17(8):367. doi: 10.3390/toxins17080367.
The venom of (BjV) induces intense and prolonged pain, which is not alleviated by antivenom, along with hemorrhage and inflammation. In this study, we investigated the effects of the specialized pro-resolving lipid mediator (SPM) maresin 2 (MaR2) in a murine model of BjV-evoked pain and inflammation. Mice received a single intraperitoneal (i.p.) injection of MaR2 30 min before the intraplantar BjV injection. MaR2 treatment significantly attenuated mechanical (electronic aesthesiometer) and thermal (hot plate) hyperalgesia in a dose-dependent manner. Additionally, MaR2 restored the balance for the hind-paw static weight distribution. When BjV (0.01, 0.1, and 1 μg) stimulus was administered intraperitoneally, pre-treatment with MaR2 (0.3, 1, or 3 ng) ameliorated mechanical and thermal hyperalgesia in a dose-dependent manner. Moreover, MaR2 (3 ng) effectively reduced the levels of myeloperoxidase activity and cytokines (TNF-α, IL-1β, and IL-6) and superoxide anion (O) production induced by intraplantar injection of BjV while enhancing total antioxidant levels (ABTS scavenging). For the peritonitis model induced by BjV, MaR2 pretreatment decreased leukocyte recruitment, hemorrhage, nitric oxide (NO), and O generation and gp91phox and inducible nitric oxide synthase (iNOS) mRNA expression. In conclusion, this study presents the first evidence that MaR2 effectively mitigated BjV-induced pain, hemorrhage, and inflammation.
（某种生物的毒液，此处未明确具体名称，用BjV指代）毒液会引发强烈且持久的疼痛，抗蛇毒血清无法缓解这种疼痛，同时还会导致出血和炎症。在本研究中，我们在BjV诱发的疼痛和炎症小鼠模型中研究了特异性促消退脂质介质（SPM）maresin 2（MaR2）的作用。小鼠在足底注射BjV前30分钟接受单次腹腔内（i.p.）注射MaR2。MaR2治疗以剂量依赖性方式显著减轻了机械性（电子麻醉计）和热性（热板）痛觉过敏。此外，MaR2恢复了后爪静态重量分布的平衡。当腹腔内给予BjV（0.01、0.1和1μg）刺激时，MaR2（0.3、1或3 ng）预处理以剂量依赖性方式改善了机械性和热性痛觉过敏。此外，MaR2（3 ng）有效降低了足底注射BjV诱导的髓过氧化物酶活性、细胞因子（TNF-α、IL-1β和IL-6）水平以及超氧阴离子（O）的产生，同时提高了总抗氧化水平（ABTS清除率）。对于BjV诱导的腹膜炎模型，MaR2预处理减少了白细胞募集、出血、一氧化氮（NO）和O的产生以及gp91phox和诱导型一氧化氮合酶（iNOS）mRNA表达。总之，本研究首次证明MaR2有效减轻了BjV诱导的疼痛、出血和炎症。
