Methanolic extract of Lippia graveolens (Mexican oregano) protects against iron- and lead-induced genomic damage without evidence of toxicity in CD-1 mice

Ethnopharmacological relevance Lippia graveolens Kunth (Mexican oregano) is traditionally used to treat gastrointestinal, respiratory, and inflammatory conditions. Its phenolic constituents provide a rationale for investigating additional biological properties, including protection against chemically induced genetic damage.Aim of the study To evaluate the antigenotoxic potential of a methanolic extract of L. graveolens against iron- and lead-induced genomic damage in CD-1 mice.Materials and methods The extract was characterized by HPLC-DAD. Acute intraperitoneal toxicity was assessed using an ascending dose design (1000-2000 mg/kg) with 14-day observation. Male CD-1 mice (n = 5/group) received the extract at 100 mg/kg under pre-treatment, co-treatment, or combined pre- and co-treatment regimens. Ferrous sulfate (72 mg/kg) or lead nitrate (98 mg/kg) was administered intraperitoneally at 0 and 24 h. Endpoints included leukocyte viability, alkaline comet assay parameters, micronucleated polychromatic erythrocyte frequency, the PCE/NCE ratio, and body weight. Between-group comparisons and paired temporal analyses were complemented by exploratory Pearson correlations.Results HPLC-DAD analysis supported the identification of galangin, chlorogenic acid, and caffeic acid by comparison with authentic standards. Acute exposure produced 50% mortality at 2000 mg/kg; a formal LD50 was not estimated. The extract alone at 100 mg/kg produced no statistically significant alterations in the evaluated endpoints. Combined pre- and co-treatment consistently produced the greatest attenuation of comet-assay damage, reducing background-corrected tail intensity by 91.0% and 85.4% for Fe and by 67.6% and 56.3% for Pb at 24 and 48 h, respectively. Micronucleus frequency was significantly reduced relative to both metal-only groups at 48 h. Responses in viability, PCE/NCE ratio, and body weight varied with treatment and sampling time. Correlations showed metal- and time-dependent associations.Conclusions The methanolic extract of L. graveolens exhibited antigenotoxic activity against Fe- and Pb-associated genomic damage, particularly under combined pre- and co-treatment. These findings identify an additional biological property under defined experimental conditions without establishing the underlying mechanisms or validating traditional therapeutic uses.