Souza Fábio A D, Spencer Patrick J, Rogero José R, Nascimento Nanci, Dal Pai-Silva Maeli, Gallacci Márcia
Departamento de Farmacologia, Instituto de Biociências, Universidade Estadual Paulista, Rubião Júnior, Botucatu, CEP 18618-000, São Paulo, Brazil.
Toxicon. 2002 Aug;40(8):1101-106. doi: 10.1016/s0041-0101(02)00103-4.
The ability of gamma radiation from 60Co (2000 Gy) to attenuate the toxic effects of Bothrops jararacussu venom was investigated on mouse neuromuscular preparations in vitro. A comparative study between the effects of native and irradiated venoms was performed on both phrenic--diaphragm (PD) and extensor digitorum longus (EDL) preparations by means of myographic, biochemical and morphological techniques. Native venom (10 and 20 micro g/ml) induced a concentration--dependent paralysis of both directly and indirectly evoked contractions on PD preparations. At 20 micro g /ml, it also caused a pronounced myotoxic effect on the EDL muscle preparation that was characterized by an increase of creatine kinase release and by several morphological changes of this preparation. By contrast, irradiated venom, even at concentrations as high as 40 micro g/ml, induced neither paralyzing nor myotoxic effects. It was concluded that 60Co gamma radiation is able to abolish both the paralyzing and the myotoxic effects of B. jararacussu venom on the mouse neuromuscular junction. These findings support the hypothesis that gamma radiation could be an important tool to improve antisera production by reducing toxicity while preserving immunogenicity.
研究了来自60Co(2000戈瑞)的γ辐射减弱巴西矛头蝮蛇毒对体外培养的小鼠神经肌肉制剂毒性作用的能力。通过肌电图、生化和形态学技术,对膈神经-膈肌(PD)和趾长伸肌(EDL)制剂上天然毒液和辐照毒液的作用进行了比较研究。天然毒液(10和20μg/ml)在PD制剂上引起直接和间接诱发收缩的浓度依赖性麻痹。在20μg/ml时,它还对EDL肌肉制剂产生明显的肌毒性作用,其特征是肌酸激酶释放增加以及该制剂的几种形态学变化。相比之下,即使辐照毒液浓度高达40μg/ml,也不会引起麻痹或肌毒性作用。得出的结论是,60Coγ辐射能够消除巴西矛头蝮蛇毒对小鼠神经肌肉接头的麻痹和肌毒性作用。这些发现支持了这样一种假设,即γ辐射可能是通过降低毒性同时保留免疫原性来提高抗血清产量的重要工具。