Abu-Sinna Gamal, Esmat Amr Y, Al-Zahaby Al Ahmady S, Soliman Nabil A, Ibrahim Tiaseer M
Department of Zoology, Faculty of Science, Ain Shams University, Cairo, Egypt.
Toxicon. 2003 Aug;42(2):207-15. doi: 10.1016/s0041-0101(03)00138-7.
In the present study fractionation of the Cerastes cerastes cerastes snake venom by gel filtration on Sephadex G-75 gave 14 protein fractions. Phospholipase PLA2 activity is not uniformly correlated with the lethality to mice in regard to all venom fractions. F11 which is the richest in PLA2 activity is less toxic than F3, which contains a small amount of PLA2, and F12 is the lowest in lethality and PLA2 activity. Treatment of Ehrlich ascites-bearing mice with two i.p. injections of the most lethal fraction (F3) or a non-lethal fraction (F4) resulted in a significant antitumor activity demonstrated by an increase in the mean survival time of the animals (22.5 and 27.9 days) and in the tumor inhibition ratio of tumor growth (T/C% 139 and 172, respectively), compared to tumor-bearing controls. The cytotoxic activity of F3 and F4 against Ehrlich ascites carcinoma cells might be due to the presence of a cytotoxin rather than to the direct cytolytic effect of the PLA2 because the non-lethal F4 is free from PLA2. Treatment of Swiss albino mice with two i.p. injections of F3 or F4 at the adopted dose levels produced no detrimental side effects demonstrated by the insignificant changes in the tested serum and liver parameters. Treatment of the tumor-bearing mice with the same venom fractions significantly modulated all of the studied biochemical parameters in the serum and liver tissues, compared to normal controls.
在本研究中,通过在葡聚糖凝胶G - 75上进行凝胶过滤对锯鳞蝰蛇毒进行分级分离,得到了14个蛋白质级分。就所有毒液级分而言,磷脂酶PLA2活性与对小鼠的致死性并非始终相关。PLA2活性最高的F11的毒性低于含有少量PLA2的F3,而F12的致死性和PLA2活性最低。对荷艾氏腹水瘤小鼠进行两次腹腔注射最具致死性的级分(F3)或非致死级分(F4)后,与荷瘤对照相比,动物平均存活时间增加(分别为22.5天和27.9天)以及肿瘤生长抑制率(T/C%分别为139和172)表明具有显著的抗肿瘤活性。F3和F4对艾氏腹水癌细胞的细胞毒性活性可能归因于一种细胞毒素的存在,而非PLA2的直接细胞溶解作用,因为非致死性的F4不含PLA2。以采用的剂量水平对瑞士白化小鼠进行两次腹腔注射F3或F4,所测血清和肝脏参数无明显变化,表明未产生有害副作用。与正常对照相比,用相同毒液级分处理荷瘤小鼠可显著调节血清和肝脏组织中所有研究的生化参数。