title: Protective effects of melatonin-loaded lipid-core nanocapsules on paraquat-induced cytotoxicity and genotoxicity in a pulmonary cell line.
abstract: Many acute poisonings lack effective and specific antidotes. Due to both intentional and accidental exposures, paraquat (PQ) causes thousands of deaths annually, especially by pulmonary fibrosis. Melatonin (Mel), when incorporated into lipid-core nanocapsules (Mel-LNC), has enhanced antioxidant properties. The effects of such a formulation have not yet been studied with respect to mitigation of PQ- induced cytotoxicity and DNA damage. Here, we have tested whether Mel-LNC can ameliorate PQ-induced toxicity in the A549 alveolar epithelial cell line. Physicochemical characterization of the formulations was performed. Cellular uptake was measured using nanocapsules marked with rhodamine B. Cell viability was determined by the MTT assay and DNA damage was assessed by the comet assay. The enzyme-modified comet assay with endonuclease III (Endo III) and formamidopyrimidine glycosylase (FPG) were used to investigate oxidative DNA damage. Incubation with culture medium for 24h did not alter the granulometric profile of Mel-LNC formulations. Following treatment (3 and 24h), red fluorescence was detected around the cell nucleus, indicating internalization of the formulation. Melatonin solution (Mel), Mel-LNC, and LNC did not have significant effects on cell viability or DNA damage. Pre-treatment with Mel-LNC enhanced cell viability and showed a remarkable reduction in % DNA in tail compared to the PQ group; this was not observed in cells pre-treated with Mel. PQ induces oxidative DNA damage detected with the enzyme-modified comet assay. Mel-LNC reduced this damage more effectively than did Mel. In summary, Mel-LNC is better than Mel at protecting A549 cells from the cytotoxic and genotoxic effects of PQ.
authors.affiliation: Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS 90610-000, Brazil; Laboratório de Toxicologia (LATOX), Faculdade de Farmácia, Universidade Federal do Rio Grandedo Sul, Porto Alegre, RS 90610-000, Brazil.
authors.forename: Mariele F
authors.initials: MF
authors.lastname: Charão
authors.affiliation: Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS 90610-000, Brazil; Laboratório de Toxicologia (LATOX), Faculdade de Farmácia, Universidade Federal do Rio Grandedo Sul, Porto Alegre, RS 90610-000, Brazil.
authors.forename: Marília
authors.initials: M
authors.lastname: Baierle
authors.affiliation: Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS 90610-000, Brazil; Laboratório de Toxicologia (LATOX), Faculdade de Farmácia, Universidade Federal do Rio Grandedo Sul, Porto Alegre, RS 90610-000, Brazil.
authors.forename: Bruna
authors.initials: B
authors.lastname: Gauer
authors.affiliation: Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS 90610-000, Brazil; Laboratório de Toxicologia (LATOX), Faculdade de Farmácia, Universidade Federal do Rio Grandedo Sul, Porto Alegre, RS 90610-000, Brazil.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Goethel
authors.affiliation: Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS 90610-000, Brazil; Laboratório de Toxicologia (LATOX), Faculdade de Farmácia, Universidade Federal do Rio Grandedo Sul, Porto Alegre, RS 90610-000, Brazil.
authors.forename: Rafael
authors.initials: R
authors.lastname: Fracasso
authors.affiliation: Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS 90610-000, Brazil; Departamento de Produção e Controle de Medicamentos, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS 90610-000, Brazil.
authors.forename: Karina
authors.initials: K
authors.lastname: Paese
authors.affiliation: Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS 90610-000, Brazil; Laboratório de Toxicologia (LATOX), Faculdade de Farmácia, Universidade Federal do Rio Grandedo Sul, Porto Alegre, RS 90610-000, Brazil.
authors.forename: Natália
authors.initials: N
authors.lastname: Brucker
authors.affiliation: Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS 90610-000, Brazil; Laboratório de Toxicologia (LATOX), Faculdade de Farmácia, Universidade Federal do Rio Grandedo Sul, Porto Alegre, RS 90610-000, Brazil.
authors.forename: Angela M
authors.initials: AM
authors.lastname: Moro
authors.affiliation: Laboratório de Toxicologia (LATOX), Faculdade de Farmácia, Universidade Federal do Rio Grandedo Sul, Porto Alegre, RS 90610-000, Brazil.
authors.forename: Guilherme B
authors.initials: GB
authors.lastname: Bubols
authors.affiliation: Laboratório de Toxicologia (LATOX), Faculdade de Farmácia, Universidade Federal do Rio Grandedo Sul, Porto Alegre, RS 90610-000, Brazil.
authors.forename: Bruna B
authors.initials: BB
authors.lastname: Dias
authors.affiliation: Centro de Terapia Gênica, Centro de Pesquisa Experimental, Hospital de Clínicas, Porto Alegre, Brazil.
authors.forename: Ursula S
authors.initials: US
authors.lastname: Matte
authors.affiliation: Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS 90610-000, Brazil; Departamento de Produção e Controle de Medicamentos, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS 90610-000, Brazil.
authors.forename: Silvia S
authors.initials: SS
authors.lastname: Guterres
authors.affiliation: Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS 90610-000, Brazil; Departamento de Química Orgânica, Instituto de Química, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS 91501-970, Brazil.
authors.forename: Adriana R
authors.initials: AR
authors.lastname: Pohlmann
authors.affiliation: Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS 90610-000, Brazil; Laboratório de Toxicologia (LATOX), Faculdade de Farmácia, Universidade Federal do Rio Grandedo Sul, Porto Alegre, RS 90610-000, Brazil. Electronic address: solange.garcia@ufrgs.br.
authors.forename: Solange C
authors.initials: SC
authors.lastname: Garcia
mesh_terms: D000975:Antioxidants / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003470:Culture Media / Q000737:chemistry; D004249:DNA Damage / Q000187:drug effects*; D006801:Humans; D008550:Melatonin / Q000494:pharmacology*; D053769:Nanocapsules / Q000737:chemistry*; D010269:Paraquat / Q000633:toxicity*; D010316:Particle Size; D011650:Pulmonary Alveoli / Q000166:cytology / Q000187:drug effects*
chemical_list: D000975:Antioxidants; D003470:Culture Media; D053769:Nanocapsules; D008550:Melatonin; D010269:Paraquat
keywords: A549 cell line; Comet assay; DNA damage; Melatonin-loaded lipid-core nanocapsules; Nanotechnology; Paraquat