Krifi M N, Marrakchi N, el Ayeb M, Dellagi K
Laboratoire de Purification des Sérums Thérapeutiques, Institut Pasteur de Tunis.
Biologicals. 1998 Dec;26(4):277-88. doi: 10.1006/biol.1998.0160.
An adequate assessment of scorpion and snake venom LD50 is an important step for accurate evaluation of antivenom sera potencies and the optimization of serotherapy. The LD50 variation of Tunisian scorpion (Androctonus australis garzonii: Aag and Buthus occitanus tunetanus: Bot) venoms with body weight, sex and strain (Swiss or C57BI/6) of mice used, the route of venom injection, the venom-milking procedures (manually or electrically) and the venom batches have been studied over a 7-year period (1990-1996). Aag venom is 3-4 times more toxic than Bot venom. However for both venoms, the LD50 determined in C57BI/6 mice, in small body weight animal or by intraperitoneal route were respectively significantly lower than those determined in Swiss mice, in high body weight or by subcutaneous route. Significant LD50 variations (25-50%) were also seen from one electrically prepared batch to another. A good correlation (r = 0.982) was observed between the concentrations of the crude venom toxic fraction determined by ELISA and LD50 values when assessed in vivo. The LD50 variation of Tunisian viper (Cerastes cerastes: Cc and Vipera lebetina: VI) venoms with the strain (Swiss or BALB/c), sex and body weight of mice used, the season and the year of venom milking were also investigated over a 3-year period (1990-1992). No significant LD50 variations were observed with the mouse strain, the sex or the season of venom milking. However, LD50 varies significantly with the year of the venom collection and the body weight of mice used. Furthermore, SDS-PAGE analysis shows annual variation for VI venom composition where no such variations were observed for Cc venom. These results stress the need either for the standardization of the venom LD50 evaluation or of the venom quality used for the development of an efficient antivenom.
对蝎毒和蛇毒的半数致死量(LD50)进行充分评估是准确评价抗蛇毒血清效力以及优化血清疗法的重要一步。在1990年至1996年的7年时间里,研究了突尼斯蝎毒(澳氏杀人蝎:Aag和北非黄肥尾蝎:Bot)的LD50随所用小鼠的体重、性别和品系(瑞士小鼠或C57BI/6小鼠)、毒液注射途径、毒液采集程序(手动或电刺激)以及毒液批次的变化情况。Aag毒液的毒性比Bot毒液高3至4倍。然而,对于这两种毒液,在C57BI/6小鼠中、小体重动物中或通过腹腔注射途径测定的LD50分别显著低于在瑞士小鼠中、大体重动物中或通过皮下注射途径测定的LD50。从一批电刺激采集的毒液到另一批,LD50也出现了显著变化(25%至50%)。通过酶联免疫吸附测定(ELISA)测定的粗毒液毒性成分浓度与体内评估的LD50值之间观察到良好的相关性(r = 0.982)。在1990年至1992年的3年时间里,还研究了突尼斯蝰蛇毒(角蝰:Cc和草原蝰:VI)的LD50随所用小鼠的品系(瑞士小鼠或BALB/c小鼠)、性别和体重、毒液采集季节以及年份的变化情况。未观察到LD?50随小鼠品系、性别或毒液采集季节的显著变化。然而,LD50随毒液采集年份和所用小鼠体重的变化显著。此外,十二烷基硫酸钠 - 聚丙烯酰胺凝胶电泳(SDS - PAGE)分析显示VI毒液成分存在年度变化,而Cc毒液未观察到此类变化。这些结果强调了对毒液LD50评估或用于开发高效抗蛇毒血清的毒液质量进行标准化的必要性。