Background

Melittin, a major component of honeybee venom, is known to possess anti-allergic, anti-inflammatory, anti-arthritis, and anti-cancer. Despite its great promise as an agent for various diseases, the therapeutic applications of melittin have been severely limited by its nonspecific cytotoxicity and hemolytic activity.

Objective

We synthesized a hybrid peptide (melittin-dKLA), composed of melittin and the pro-apoptotic peptide (dKLA), and evaluated its potential toxicity in ICR mice following a single or repeated subcutaneous dose administration.

Results

Mice administered a single subcutaneous dose of melittin-dKLA showed no mortality or abnormal clinical signs in all animals. Similarly, mice administered a repeated subcutaneous dose of melittin-dKLA resulted in no deaths. Crust formation and induration were observed in the male and female mice in the 5 and 20 mg/kg, respectively. The hematological parameters and serum biochemical analysis did not show any changes by melittin-dKLA. In repeated subcutaneous dose study, the mice in the 20 mg/kg group showed a significant increase in the relative weight of the spleen compared to the control group. Although the difference was not statistically significant. Mice exhibited a common pattern of change.

Conclusion

Taken together, our results suggest that the toxicity of melittin-dKLA is higher than 20 mg/kg both as a single and a repeated subcutaneous administration in ICR mice. Thus, it is suggested that it will be an important data in the development of new drug for melittin-dKLA.

中文翻译：

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蜂毒肽-dKLA在ICR小鼠中的皮下毒性

背景

蜂毒肽是蜜蜂毒液的主要成分，已知具有抗过敏、抗炎、抗关节炎和抗癌作用。尽管蜂毒肽作为治疗各种疾病的药物前景广阔，但其非特异性细胞毒性和溶血活性严重限制了蜂毒肽的治疗应用。

客观的

我们合成了一种混合肽（蜂毒肽-dKLA），由蜂毒肽和促凋亡肽 (dKLA) 组成，并在单次或重复皮下给药后评估了其对 ICR 小鼠的潜在毒性。

结果

在所有动物中，给予单一皮下剂量的蜂毒肽-dKLA 的小鼠均未出现死亡或异常临床症状。类似地，给小鼠重复皮下注射蜂毒肽-dKLA 没有导致死亡。在雄性和雌性小鼠中分别观察到 5 和 20 mg/kg 的结壳形成和硬结。蜂毒肽-dKLA 的血液学参数和血清生化分析未显示任何变化。在重复皮下剂量研究中，与对照组相比，20 mg/kg 组小鼠的脾脏相对重量显着增加。虽然差异没有统计学意义。小鼠表现出一种共同的变化模式。

结论

总之，我们的结果表明，在 ICR 小鼠中，作为单次和重复皮下给药，蜂毒肽-dKLA 的毒性均高于 20 mg/kg。因此，这将成为开发蜂毒肽-dKLA新药的重要数据。