载有褪黑素的脂质核纳米胶囊通过增加秀丽隐杆线虫 SOD 的表达来对抗百草枯引起的脂质过氧化。
Melatonin-loaded lipid-core nanocapsules protect against lipid peroxidation caused by paraquat through increased SOD expression in Caenorhabditis elegans.
机构信息
Laboratory of Toxicology (LATOX), Federal University of Rio Grande do Sul, Porto Alegre, Brazil, Porto Alegre, Rio Grande do Sul, Brazil.
Laboratory of Analytical Toxicology, Feevale University, Novo Hamburgo, Brazil, Novo Hamburgo, RS, Brazil.
出版信息
BMC Pharmacol Toxicol. 2019 Dec 19;20(Suppl 1):80. doi: 10.1186/s40360-019-0352-4.
BACKGROUND
Melatonin has been described in the literature as a potent antioxidant. However, melatonin presents variable, low bioavailability and a short half-life. The use of polymeric nanoparticulated systems has been proposed for controlled release. Thus, the purpose of this study was to investigate the action of melatonin-loaded lipid-core nanocapsules (Mel-LNC) in the antioxidant system of Caenorhabditis elegans, and the possible protective effect of this formulation against lipid peroxidation caused by paraquat (PQ).
METHODS
The suspensions were prepared by interfacial deposition of the polymer and were physiochemically characterized. C. elegans N2 wild type and transgenic worm CF1553, muls84 [sod-3p::gfp; rol6(su1006)] were obtained from the Caenorhabditis Genetics Center (CGC). The worms were divided into 5 groups: Control, PQ 0.5 mM, PQ 0.5 mM + Mel-LNC 10 μg/mL, PQ + unloaded lipid-core nanocapsules (LNC), and PQ + free melatonin (Mel) 10 μg/mL. The lipid peroxidation was assessed through thiobarbituric acid (TBARS) levels and the fluorescence levels of the transgenic worms expressing GFP were measured.
RESULTS
The LNC and Mel-LNC presented a bluish-white liquid, with pH values of 5.56 and 5.69, respectively. The zeta potential was - 6.4 ± 0.6 and - 5.2 ± 0.2, respectively. The mean particle diameter was 205 ± 4 nm and 203 ± 3 nm, respectively. The total melatonin content was 0.967 mg/ml. The TBARS levels were significantly higher in the PQ group when compared to the control group (p < 0.001). Mel-LNC reduced TBARS levels to similar levels found in the control group. Moreover, only Mel-LNC significantly enhanced the SOD-3 expression (p < 0.05). Mel-LNC was capable of protecting C. elegans from lipid peroxidation caused by PQ and this was not observed when free melatonin was used. Moreover, Mel-LNC increased the fluorescence intensity of the transgenic strain that encodes the antioxidant enzyme SOD-3, demonstrating a possible mechanism of protection from PQ-induced damage.
CONCLUSION
These findings demonstrated that melatonin, when associated with nanocapsules, had improved antioxidant properties and the protective activity against PQ-induced lipid peroxidation could be associated with the activation of antioxidant enzymes by Mel-LNC in C. elegans.
背景
褪黑素在文献中被描述为一种有效的抗氧化剂。然而，褪黑素的生物利用度低，半衰期短。聚合物纳米颗粒系统的使用已被提出用于控制释放。因此，本研究的目的是研究负载褪黑素的脂质核纳米囊泡（Mel-LNC）在秀丽隐杆线虫抗氧化系统中的作用，以及该制剂对百草枯（PQ）引起的脂质过氧化的可能保护作用。
方法
通过聚合物的界面沉积制备混悬液，并进行理化特性表征。秀丽隐杆线虫 N2 野生型和转基因虫 CF1553、muls84 [ sod-3p::gfp； rol6(su1006)] 从秀丽隐杆线虫遗传中心（CGC）获得。将蠕虫分为 5 组：对照组、PQ 0.5 mM、PQ 0.5 mM+10μg/mL Mel-LNC、PQ+未负载脂质核纳米囊泡（LNC）和 PQ+10μg/mL 游离褪黑素（Mel）。通过硫代巴比妥酸（TBARS）水平评估脂质过氧化，并用表达 GFP 的转基因蠕虫的荧光水平进行测量。
结果
LNC 和 Mel-LNC 呈现出蓝白色液体，pH 值分别为 5.56 和 5.69。zeta 电位分别为-6.4±0.6 和-5.2±0.2。平均粒径分别为 205±4nm 和 203±3nm。总褪黑素含量为 0.967mg/ml。与对照组相比，PQ 组的 TBARS 水平显著升高（p<0.001）。Mel-LNC 降低 TBARS 水平至与对照组相似的水平。此外，只有 Mel-LNC 显著增强了 SOD-3 的表达（p<0.05）。Mel-LNC 能够保护秀丽隐杆线虫免受 PQ 引起的脂质过氧化，而游离褪黑素则没有观察到这种作用。此外，Mel-LNC 增加了编码抗氧化酶 SOD-3 的转基因菌株的荧光强度，表明其具有保护秀丽隐杆线虫免受 PQ 诱导损伤的可能机制。
结论
这些发现表明，褪黑素与纳米囊泡结合后具有改善的抗氧化特性，其对 PQ 诱导的脂质过氧化的保护活性可能与 Mel-LNC 在秀丽隐杆线虫中激活抗氧化酶有关。
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