Melatonin-loaded lipid-core nanocapsules protect against lipid peroxidation caused by paraquat through increased SOD expression in Caenorhabditis elegans

被引:19
作者
Charao, Mariele F. [1 ,2 ]
Goethel, Gabriela [1 ,3 ]
Brucker, Natalia [1 ,4 ]
Paese, Karina [3 ]
Eifler-Lima, Vera L. [3 ]
Pohlmann, Adriana R. [3 ]
Guterres, Silvia S. [3 ]
Garcia, Solange C. [1 ,3 ]
机构
[1] Univ Fed Rio Grande do Sul, Lab Toxicol LATOX, Porto Alegre, RS, Brazil
[2] Feevale Univ, Lab Analyt Toxicol, Novo Hamburgo, RS, Brazil
[3] Univ Fed Rio Grande do Sul, Postgrad Program Pharmaceut Sci, Porto Alegre, RS, Brazil
[4] Univ Fed Santa Maria, Dept Physiol & Pharmacol, Santa Maria, RS, Brazil
关键词
Nanocapsules; Antioxidant; C; elegans; Herbicide; Superoxide dismutase; MN-INDUCED TOXICITY; OXIDATIVE-STRESS; INDUCED CYTOTOXICITY; POLYMERIC WALL; DNA-DAMAGE; NANOPARTICLES; STRATEGY; IMPROVES; BRAIN; ASSAY;
D O I
10.1186/s40360-019-0352-4
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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 mu g/mL, PQ + unloaded lipid-core nanocapsules (LNC), and PQ + free melatonin (Mel) 10 mu g/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.
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页数:7
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