Phytochemical Composition and Protective Effect of Leaf against In Vivo Doxorubicin-Mediated Toxicity.

(Spreng.) A.J. Vega & Dematt. (syn.: Less) is popularly known as "assa-peixe" and its leaves are used in folk medicine mainly to treat respiratory diseases. In this study, we evaluated the cytogenotoxic and anticytogenotoxic potential of the leaf aqueous extract (LAE) and its -butanol fraction (BF) in the presence or absence of doxorubicin (DXR) (pre-, co-, and post-treatments) on a murine model for 24 h or 120 h. The micronucleus test (MN) and the comet assay were used to assess the cytogenotoxic and anticytogenotoxic potential of LAE and BF (250, 500, and 1000 mg/kg) administered via gavage to Swiss Webster mice. The chemical profiles of LAE and BF were assessed by liquid chromatography coupled to mass spectrometry, and their metabolites were putatively identified. Lastly, the possible biological activities related to the (anti) cytogenotoxicity of the compounds were predicted using the PASS online webserver. The in vivo results showed that different doses of LAE and BF did not present cytotoxic activity; however, the MN test revealed a slight mutagenic activity for the 24 h treatments. Moderate genotoxic effects were demonstrated for all treatments in the comet assay. Regarding anticytotoxicity and antimutagenicity, LAE and BF presented a high cytoprotective potential against DXR toxic effects. In the co-treatment, LAE reduced the DXR genotoxicity by ~27%, and -BF did not demonstrate antigenotoxic potential. In contrast, an antigenotoxic effect was observed for both LAE and -BF in the pre- and post-treatments, reducing DXR genotoxicity by ~41% and ~47%, respectively. Chemical analysis of LAE and BF showed the presence of eight phenolic compounds, including seven chlorogenic acids and a flavonoid. The PASS online tool predicted antimutagenic, anticancer, antineoplastic, chemoprotective, antioxidant, and radical scavenging activities for all constituents identified in LAE and -BF. leaves presented a protective effect against DXR cytogenotoxicity. In general, LAE and -BF showed a greater antigenotoxic potential in the pre- and post-treatments. The metabolites putatively identified in LAE and -BF exhibited antioxidant and chemoprotective potential according to computational prediction analysis. Altogether, our results highlight the potential application of to protect against toxic manifestations induced by DXR.