title: Citral and eugenol modulate DNA damage and pro-inflammatory mediator genes in murine peritoneal macrophages.
abstract: Citral and eugenol have been broadly studied because of their anti-inflammatory, antioxidant and antiparasitic potentials. In this study, the effects of citral (25, 50 and 100 µg/mL) and eugenol (0.31, 0.62, 1.24 and 2.48 µg/mL) on the expression (RT-PCR) of the pro-inflammatory mediator genes NF-κB1, COX-2 and TNF-α were evaluated in mouse peritoneal macrophages with or without activation by a bacterial lipopolysaccharide (LPS). Additionally, the genotoxic potentials of two compounds and their capacities to modulate the DNA damage induced by doxorubicin (DXR) were investigated using the comet assay. The data revealed that neither citral nor eugenol changed COX-2, NF-κB1 or TNF-α expression in resting macrophages. However, in LPS-activated cells, citral induced the hypoexpression of COX-2 (100 µg/mL) and TNF-α (50 and 100 µg/mL). Hypoexpression of TNF-α was also detected after cellular exposure to eugenol at the highest concentration (2.48 µg/mL). Both compounds exhibited genotoxic potential (citral at 50 and 100 µg/mL and eugenol at all concentrations) but also showed chemopreventive effects, in various treatment protocols. Both citral and eugenol might modulate inflammatory processes and DXR-induced DNA damage, but the use of these compounds must be viewed with caution because they are also able to induce primary DNA lesions.
authors.affiliation: Departamento de Patologia, Faculdade de Medicina de Botucatu, UNESP - Universidade Estadual Paulista, Botucatu, SP, 18618-000, Brazil, mpporto@gmail.com.
authors.forename: Marilia de Paula
authors.initials: Mde P
authors.lastname: Porto
authors.forename: Glenda Nicioli
authors.initials: GN
authors.lastname: da Silva
authors.forename: Bruno Cesar Ottoboni
authors.initials: BC
authors.lastname: Luperini
authors.forename: Tatiana Fernanda
authors.initials: TF
authors.lastname: Bachiega
authors.forename: João Paulo
authors.initials: JP
authors.lastname: de Castro Marcondes
authors.forename: José Maurício
authors.initials: JM
authors.lastname: Sforcin
authors.forename: Daisy Maria Fávero
authors.initials: DM
authors.lastname: Salvadori
mesh_terms: D000080462:Acyclic Monoterpenes; D000704:Analysis of Variance; D000818:Animals; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004249:DNA Damage / Q000187:drug effects / Q000502:physiology*; D017931:DNA Primers / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D005054:Eugenol / Q000494:pharmacology* / Q000633:toxicity; D005786:Gene Expression Regulation / Q000187:drug effects*; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D039821:Monoterpenes / Q000494:pharmacology* / Q000633:toxicity; D009152:Mutagenicity Tests; D016328:NF-kappa B / Q000378:metabolism; D010537:Peritoneum / Q000166:cytology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000080462:Acyclic Monoterpenes; D017931:DNA Primers; D039821:Monoterpenes; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D005054:Eugenol; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; C007076:citral
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