Protective effects of melatonin-loaded lipid-core nanocapsules on paraquat-induced cytotoxicity and genotoxicity in a pulmonary cell line

Charão, Mariele Feiffer; Baierle, Marília; Gauer, Bruna; Göethel, Gabriela; Fracasso, Rafael; Paese, Karina; Brucker, Natália; Moro, Ângela M.; Bubols, Guilherme Borges; Dias, Bruna Bernar; Matte, Úrsula; Guterres, Sílvia Stanisçuaski; Pohlmann, Adriana Raffin; Garcia, Solange Cristina

doi:10.1016/j.mrgentox.2015.04.006

Cited by 28 publications

(13 citation statements)

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“…Schaffazick et al [9] demonstrated that the encapsulation of melatonin, in polymeric nanocapsules, improved the antioxidant properties of this molecule as it caused a reduction in lipid peroxidation in the brain and liver of Wistar rats. Recently, our research group reported that melatonin-loaded lipid-core nanocapsules (Mel-LNC), prepared with PCL, presented protective effects against cytotoxicity and genotoxicity caused by paraquat (PQ) in the A549 cell line [10] and reduced ROS production in Caenorhabditis elegans exposed to PQ [11].…”

Section: Introductionmentioning

confidence: 99%

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

Charão

Göethel

Brucker

et al. 2019

BMC Pharmacol Toxicol

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BackgroundMelatonin 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).MethodsThe 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.ResultsThe 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.ConclusionThese 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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Section: Introductionmentioning

confidence: 99%

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

Charão

Göethel

Brucker

et al. 2019

BMC Pharmacol Toxicol

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“…17,18 Additionally, the cellular uptake was demonstrated in the A549 cell line, indicating the internalization of this type of LNC. 19 The rapid increase of nanotechnology has stimulated the use of methodologies to assess the toxicological profile of nanomaterials. 20 The toxicity evaluation of nanomaterials is currently becoming detrimental, once their safety is necessary for future application.…”

Section: Introductionmentioning

confidence: 99%

Caenorhabditis elegans as an alternative in vivo model to determine oral uptake, nanotoxicity, and efficacy of melatonin-loaded lipid-core nanocapsules on paraquat damage

Charão

Souto

Brucker

et al. 2015

IJN

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Caenorhabditis elegans is an alternative in vivo model that is being successfully used to assess the pharmacological and toxic effects of drugs. The exponential growth of nanotechnology requires the use of alternative in vivo models to assess the toxic effects of theses nanomaterials. The use of polymeric nanocapsules has shown promising results for drug delivery. Moreover, these formulations have not been used in cases of intoxication, such as in treatment of paraquat (PQ) poisoning. Thus, the use of drugs with properties improved by nanotechnology is a promising approach to overcome the toxic effects of PQ. This research aimed to evaluate the absorption of rhodamine B-labeled melatonin (Mel)-loaded lipid-core nanocapsules (LNC) by C. elegans , the application of this model in nanotoxicology, and the protection of Mel-LNC against PQ damage. The formulations were prepared by self-assembly and characterized by particle sizing, zeta potential, drug content, and encapsulation efficiency. The results demonstrated that the formulations had narrow size distributions. Rhodamine B-labeled Mel-LNC were orally absorbed and distributed in the worms. The toxicity assessment of LNC showed a lethal dose 50% near the highest dose tested, indicating low toxicity of the nanocapsules. Moreover, pretreatment with Mel-LNC significantly increased the survival rate, reduced the reactive oxygen species, and maintained the development in C. elegans exposed to PQ compared to those worms that were either untreated or pretreated with free Mel. These results demonstrated for the first time the uptake and distribution of Mel-LNC by a nematode, and indicate that while LNC is not toxic, Mel-LNC prevents the effects of PQ poisoning. Thus, C. elegans may be an interesting alternative model to test the nanocapsules toxicity and efficacy.

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“…Charao et al have shown significant antioxidant property of melatonin in paraquat poisoning [13]. The oxidative injuries of paraquat have also been demonstrated due to its chronic exposure [14][15][16][17][18].…”

Section: Discussionmentioning

confidence: 99%

Prevention of Lung Complications following Paraquat Poisoning by Silymarin, N-acetyl Cysteine and Hydrocortisone: An Experimental Study

Solhi

Ghasemi

Rahbari

et al. 2020

IJT

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Background: Paraquat poisoning results in multi-organ failure, primarily pulmonary fibrosis, acute renal failure, and hepatic impairment. The present study was designed to evaluate three treatment regimens, such as N-Acetyl cysteine (NAC), silymarin and hydrocortisone in the prevention of lung fibrosis after ingestion of toxic doses of paraquat in rats. Methods: Male Sprague-Dawley rats (N=20) were randomly divided into four groups of five each. The drugs and paraquat were given to the rats orally. All rat groups received one oral dose of paraquat (10 mg/kg) once daily for 1 week. The first group received a daily oral dose of silymarin (600 mg/kg) for 2 weeks. The second group received a daily oral dose of NAC (500 mg/kg) for 2 weeks. The third group was given daily oral doses of NAC (500 mg/kg) and hydrocortisone (50 mg/kg) for 2 weeks. The fourth group (controls) received no drugs other than paraquat. The experiment continued for 4 weeks. After the experiment, autopsy was performed on all rats and the lungs were examined histopathologically. Results: The results of histopathology examinations for peribronchial inflammation in the groups were shown that NAC plus hydrocortisone and silymarin had notable effects in the prevention of lung inflammation. Septal widening in the lungs was also observed in group three less than that in the other groups. Conclusion: Based on the results, silymarin, NAC and hydrocortisone may be used as a palliative treatment in paraquat poisoning specifically aimed at preventing the acute and chronic lung injuries as the worst complication of the poisoning.

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Protective effects of melatonin-loaded lipid-core nanocapsules on paraquat-induced cytotoxicity and genotoxicity in a pulmonary cell line

Cited by 28 publications

References 44 publications

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

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

Caenorhabditis elegans as an alternative in vivo model to determine oral uptake, nanotoxicity, and efficacy of melatonin-loaded lipid-core nanocapsules on paraquat damage

Prevention of Lung Complications following Paraquat Poisoning by Silymarin, N-acetyl Cysteine and Hydrocortisone: An Experimental Study

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