Study the Safety Evaluation and Immunotoxicity of Empty-Nanocapsules by Oral Feeding on Mice

• Main Authors: Chang,Yi-Yun, 張議云
• Other Authors: Wu,Wen-Mein
• Format: Others
• Language: zh-TW
• Published: 2008
• Online Access: http://ndltd.ncl.edu.tw/handle/52851029481506044496

碩士 === 輔仁大學 === 營養科學系 === 96 === Nanoparticles or nanocapsules could increase the stability, absorption and release of the bioactivity ingredients. However, the safety, bioavailability and potential toxicity of nanomaterials should be concerned. Male ICR mice were administrated three different dosages of empty-nanocapsules (1N: 150 mg/kg BW; 5N: 750 mg/kg BW; 10N: 1500 mg/kg BW) or non-treatment (control group) by orally feeding. We evaluated the safety of empty-nanocapsules by micronucleus test for estimating the gene toxicity, and the oral acute toxicity test. Seven days later, mice were scarified and the effects of nanocapsules on the immune system was analyzed for evaluating their intestinal and systemic immunity. All dosages of nanocapsule exhibited non-detectable genetoxicity in vivo on erythrocyte micronuclei assay. Nanocapsules show no gene toxicity and no observable changes of behavior in the present study. In addition, there was no significant difference in body weight among four groups. The weights of spleens were significantly decreased in the 5N group compared to the control group. Beside the spleen, there were no significant difference in organ, the percentage of organ and its relative weight, hematological examination, blood biomarker assay was noted compared with control. In the study of intestinal immunity, the B cell proliferate response of Peyer’s patches (PP) was decreased in the 1N group compared to the non-treated group. Besides, mice fed with 5N nanocapsule could increase the T cell proliferate response of mesenteric lymph node (MLN), the percentage of CD4+ T cell and CD8+ T cell subpopulation. On evaluation of the systemic immunity, the 5N nanocapsule- feeding resulted higher phagocytic activity of blood granulocytes and natural killer cell (NK) activity of splenocyte significantly. The 10N nanocapsule-feeding group had shown reduced nitric oxide (NO) production of peritoneal exudates cell (PEC) as compared to the control group. There was no difference on the level of IL-6 secreted by PEC among four groups. As elevated phagocytic activity and NK activity are associated with predominant TH1 immune response, in our study mice fed with 1N and 5N nanocapsules seem promote the immune response towards TH1 which was identified by increase the ratio of IFN-γ to IL-4. However, the 10N nanocapsule-feeding group resulted in the immune response towards TH2 response. Splenocyte stimulated by mitogen (Con A or LPS) significantly increased the proliferation response of T and B cell in the nanocapsule- feeding group compared to the control group. It appeared higher percentage of CD8+ T cell in the 1N group, and higher percentage of CD4+ T cell in splenocytes of 5N group than in the control group. Our data supported that the lower dosage (1N) of nanocapsule-feeding could increase the cell numbers of CD8+ T cell and suppressed the secretion of IL-4. In 5N dosage of nanocapsule-feeding group, it could increase the population of CD4+ T cell, promoted phagocytic activity and NK cell activity. Collected data suggested that mice fed with the 1N and 5N dosages of nanocapsule may have beneficial for promoting innate immune response in ICR mice. In conclusion, male ICR mice fed with empty-nanocapsules for 7 days shown non-genetoxicity and non-acute toxicity, and it may achieve the immunomodulating capacity through regulating the activity of T cell function during short-term (7 days) treatment. We proposed that empty-nanocapsules may up-regulating the T cell activity in MLN, then followed T cell migration into the nearby lymph fluid and play some roles on controlling the systemic immune response.