关键词: In vitro In vivo Nanomedicine Plasmodium Treatment

Mesh : Animals Acyclic Monoterpenes / pharmacology Zinc Oxide / pharmacology administration & dosage chemistry Mice Plasmodium berghei / drug effects Antimalarials / pharmacology administration & dosage Nanoparticles / chemistry Oxidative Stress / drug effects Plasmodium falciparum / drug effects Monoterpenes / pharmacology administration & dosage chemistry Malaria / drug therapy Cytokines / metabolism Disease Models, Animal Male Antioxidants / pharmacology administration & dosage Drug Carriers / chemistry

来  源:   DOI:10.1016/j.actatropica.2024.107312

Abstract:
This research aimed to produce and analyze zinc oxide nanoparticles (ZNPs) loaded with linalool (LZNPs), and to evaluate their in vitro and in vivo efficacy through targeting the inflammation and oxidative stress. LZNPs were synthesized using an ethanolic solution of polyvinyl alcohol. The Malstat technique was used to evaluate the effectiveness of LZNPs against both sensitive and resistant strains of Plasmosium falciparum. In vivo effects of ZNPs and LZNPs on parasite growth suppression, survival rate, oxidative stress markers, antioxidant genes, and gene and protein levels of inflammatory cytokines were evaluated by Real-time PCR and Western blot techniques. The results indicated that LZNPs demonstrated noteworthy (P < 0.001) antiplasmodial activity against both susceptible and resistant strains of P. falciparum. P. berghei NK65 strain-infected mice treated with the ZNPs and LZNPs at doses of 5-15 mg/kg notably (p < 0.001) increased the survival rates and parasite growth suppression. LZNPs at 5-15 mg/kg demonstrated a significant (p < 0.001) decrease in oxidative stress markers, increased the expression level of antioxidant genes, and reduced the gene and protein expression level of inflammatory cytokines. The current experimental study demonstrated the potent in vitro antiplasmodial activity of LZNPs against chloroquine-resistant and sensitive strains of P. falciparum compared to ZNPs alone. Additionally, the study identified the potential benefits of this nanocomposite in suppressing the parasite and extending the survival rate in mice infected with P. berghei by targeting inflammation and oxidative stress. It also showed minimal toxicity in liver and kidney function in healthy mice. Nevertheless, further research is essential to elucidate the comprehensive mechanisms and practical effectiveness of LZNPs.
摘要:
本研究旨在生产和分析负载芳樟醇(LZNPs)的氧化锌纳米粒子(ZNPs),并通过靶向炎症和氧化应激来评估其体外和体内功效。使用聚乙烯醇的乙醇溶液合成LZNP。Malstat技术用于评估LZNP对恶性疟原虫敏感和抗性菌株的有效性。ZNPs和LZNPs对寄生虫生长抑制的体内作用,存活率,氧化应激标志物,抗氧化基因,通过Real-timePCR和Westernblot技术评价炎性细胞因子的基因和蛋白水平。结果表明,LZNP对恶性疟原虫的易感和抗性菌株均表现出值得注意的(P<0.001)抗疟药活性。用剂量为5-15mg/kg的ZNP和LZNP处理的BergheiNK65菌株感染的小鼠显著(p<0.001)增加了存活率和寄生虫生长抑制。LZNPs在5-15mg/kg时显示出氧化应激标志物的显著降低(p<0.001),增加了抗氧化基因的表达水平,降低炎性细胞因子的基因和蛋白表达水平。目前的实验研究表明,与单独的ZNP相比,LZNP对恶性疟原虫的氯喹抗性和敏感菌株具有有效的体外抗疟原虫活性。此外,该研究确定了这种纳米复合材料通过靶向炎症和氧化应激在抑制寄生虫和延长感染伯氏疟原虫的小鼠存活率方面的潜在益处。它对健康小鼠的肝和肾功能也显示出最小的毒性。然而,进一步的研究对于阐明LZNP的综合机制和实际有效性至关重要。
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