Citral and eugenol modulate DNA damage and pro-inflammatory mediator genes in murine peritoneal macrophages

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 mu g/mL) and eugenol (0.31, 0.62, 1.24 and 2.48 mu g/mL) on the expression (RT-PCR) of the pro-inflammatory mediator genes NF-kappa B1, COX-2 and TNF-alpha 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-kappa B1 or TNF-alpha expression in resting macrophages. However, in LPS-activated cells, citral induced the hypoexpression of COX-2 (100 mu g/mL) and TNF-a (50 and 100 mu g/mL). Hypoexpression of TNF-alpha was also detected after cellular exposure to eugenol at the highest concentration (2.48 mu g/mL). Both compounds exhibited genotoxic potential (citral at 50 and 100 mu g/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.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP