Department of Clinical Pharmacy, Faculty of Pharmacy, Jordan University of Science and Technology, P.O. Box 3030, Irbid, 22110, Jordan.
Research and Innovation Centre, The Jordanian Pharmaceutical Manufacturing Company, Amman, Jordan.
Toxicon. 2019 Aug;166:1-8. doi: 10.1016/j.toxicon.2019.05.006. Epub 2019 May 13.
Vipera palaestinae is responsible for many venomous incidents in the Middle East. However, this species is not included in the antigenic pool of venoms for the production of the regionally available polyvalent antivenoms. In an attempt to develop a potential complementary alternative therapy for snakebite patients, this study is investigating the antagonistic effect of Eryngium creticum against V. palaestinae venom. In this context, the concentration of the venom as well as the electrophoretic profile, and the venom LD were determined by intraperitoneal injection (ip). The methanolic leaf extract was prepared, and its safety on rats was examined. Adult male Sprague-Dawley rats were divided into 8 groups (n = 6); G1-G3 were injected subplantar in the right hind paws with 2.5, 3.125, and 3.75 mg kg then 200 mg kg extract ip. G4-G6 were given the same venom dose with no extract, respectively. Controls were G7 that only had the extract ip, and G8 that was injected subplantar with PBS. The swollen paws were measured at Hour 0 (before injection), Hour 1, Hour 6, and Hour 24. IL-6 and TNF-α were measured in serum using ELISA. Histopathological changes were examined in paw sections. The pooled venom concentration was 176.93 ± 35.81 mg ml, revealed 10 protein bands (5-80 kDa), and the LD via ip rout was 6.56 mg kg. Paw edema peaked at Hour 1. At Hour 6, edema in G1 was significantly reduced (p < 0.05) compared to G6, while at Hour 24 there was no significant difference between all groups including the controls. Treated animals in G1-G3 expressed IL-6 significantly lower (p < 0.001) than untreated G4-G6, respectively. Levels of TNF-α in G1 and G2 were significantly (p < 0.001) lower than G3-G6, while G5 and G6 were significantly (p < 0.001) higher than G1-G4. Histopathological changes showed intensifying edema, hemorrhage, and inflammation with incrementing venom doses. Sections from treated animals expressed less adverse changes compared to untreated animals. Together, the outcomes are encouraging future utilization of E. creticum as a supportive remedy for snakebite cases.
巴勒斯坦蝰蛇在中东地区引发了许多毒液事件。然而，这种蛇种并不包含在该地区多价抗蛇毒血清的抗原池中。为了为蛇咬伤患者开发一种潜在的互补替代疗法，本研究调查了刺山柑对巴勒斯坦蝰蛇毒液的拮抗作用。在这种情况下，通过腹腔注射（ip）确定毒液的浓度、电泳图谱和毒液 LD。制备了甲醇叶提取物，并检查了其对大鼠的安全性。成年雄性 Sprague-Dawley 大鼠分为 8 组（n=6）；G1-G3 在右后爪跖皮下注射 2.5、3.125 和 3.75 mg/kg ，然后注射 200 mg/kg 提取物 ip。G4-G6 分别给予相同剂量的毒液但不给予提取物。对照 G7 仅给予提取物 ip，G8 给予 PBS 皮下注射。在注射前（Hour 0）、Hour 1、Hour 6 和 Hour 24 测量肿胀的爪子。使用 ELISA 测量血清中的 IL-6 和 TNF-α。检查爪子切片中的组织病理学变化。混合毒液浓度为 176.93±35.81mg/ml，显示 10 条蛋白带（5-80kDa），通过 ip 途径的 LD 为 6.56mg/kg。爪肿胀在 Hour 1 达到峰值。在 Hour 6 时，与 G6 相比，G1 的肿胀明显减少（p<0.05），而在 Hour 24 时，包括对照组在内的所有组之间没有显著差异。与未处理的 G4-G6 相比，处理动物 G1-G3 表达的 IL-6 显著降低（p<0.001）。与 G3-G6 相比，G1 和 G2 中的 TNF-α 水平显著降低（p<0.001），而 G5 和 G6 显著高于 G1-G4。组织病理学变化显示随着毒液剂量的增加，水肿、出血和炎症加剧。与未处理的动物相比，处理动物的切片表达的不良反应较少。总之，这些结果令人鼓舞，未来可将刺山柑用作蛇咬伤病例的辅助治疗方法。
