Laboratório de Bioquímica e Microbiologia Aplicada, Instituto de Ciência e Tecnologia de Alimentos, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
Int J Pharm. 2011 Dec 12;421(1):94-8. doi: 10.1016/j.ijpharm.2011.09.020. Epub 2011 Sep 21.
Immunogenicity and toxicity of antimicrobial peptide P34 were evaluated in vivo. BALB/c mice were inoculated intraperitoneally with peptide P34 alone and associated with Freund's adjuvant. For acute toxicity testing, different concentrations of the peptide P34 (82.5, 165.0, 247.5 and 330.0mg/kg) were orally administered. To evaluate the sub-chronic toxicity the tested dose of 0.825 mg/kg/day of the peptide P34 or nisin were administered for 21 days. There were no hypersensitivity reactions or significant increase in antibody titer during the immunogenicity experiment or death of animals during the acute or sub-chronic toxicity tests. The LD(50) was higher than 332.3 ± 0.76 mg/kg. No significant changes in serum biochemical parameters were observed in the animals treated with the peptide P34 unlike nisin-treated group showed a significant increase in alanine transaminase levels in comparison to controls. The group treated with 0.825 mg/kg/day of nisin showed histological changes in the spleen, skin and liver. In the group treated with peptide P34 histological changes in the spleen were observed, with the presence of megakaryocytes. Few studies report the use of animal models to evaluate the in vivo toxicity of antimicrobial peptides and such investigation is an essential step to ensure it safe use in foods.
抗菌肽 P34 的免疫原性和毒性在体内进行了评估。BALB/c 小鼠经腹腔单独接种肽 P34 并与弗氏佐剂联合接种。为了进行急性毒性试验，口服不同浓度的肽 P34（82.5、165.0、247.5 和 330.0mg/kg）。为了评估亚慢性毒性，以 0.825mg/kg/天的肽 P34 或乳链菌肽的测试剂量给药 21 天。在免疫原性实验期间没有过敏反应或抗体滴度显著增加，在急性或亚慢性毒性试验期间也没有动物死亡。LD（50）大于 332.3 ± 0.76mg/kg。与乳链菌肽处理组相比，用肽 P34 处理的动物的血清生化参数没有显著变化，而乳链菌肽处理组的丙氨酸转氨酶水平显著升高。以 0.825mg/kg/天剂量的乳链菌肽治疗的组在脾脏、皮肤和肝脏中显示出组织学变化。用肽 P34 治疗的组观察到脾脏组织学变化，存在巨核细胞。很少有研究报告使用动物模型来评估抗菌肽的体内毒性，这种研究是确保其在食品中安全使用的必要步骤。
