Dados do Resumo

Título

CYTOTOXIC, GENOTOXIC AND ANTIOXIDANT EVALUATION OF CAFFEIC ACID IN PRECLINICAL STUDIES

Introdução

Caffeic acid (CA) is a polyphenol belonging to the phenylpropanoid family, commonly found in plants. Research has revealed several health benefits associated with CA, including its antioxidant, anti-inflammatory, and anticancer properties. These effects are attributed to its ability to modulate several pathways, such as inhibition of NFkB, STAT3, and ERK1/2, thereby reducing inflammatory responses, and activation of the Nrf2/ARE pathway to enhance cellular antioxidant defenses.

Objetivo

Thus, the present study evaluated the toxicity, cytotoxicity, genotoxicity and antioxidant potential of isolated caffeic acid and in association with Doxorrubicina (DOX) in studies in vitro .

Métodos

Toxicity tests were performed with the Artemia salina bioassay, determination of total antioxidant activity was performed by capturing the DPPH free radical, and DNA fragmentation by agarose gel electrophoresis and MTT cell viability assay were performed in cell culture of murine melanoma (B16F10) and human breast cancer (MDA-MB-231).

Resultados

CA was tested at concentrations of 1000 to 31.25 µg/ml for the proposed tests. The Artemia salina test of CA did not show significant toxicity, where the highest concentration (1000 µM) showed only 30% toxicity. Therefore, the LC50 of CA could not be calculated and was considered as a non-toxic phytochemical. In the DNA fragmentation (48h), a strongly marked band of intact DNA was observed, with low DNA fragmentation (smear) at the CA tested concentrations (500, 250 and 100 µg/ml). Treatment with 30 µg/ml of DOX in association with CA, the intact bands of genomic DNA diminished, caused by the expected DOX genotoxicity. Higher CA concentrations modulated the DOX DNA damage. Regarding the MTT assay, it was found that caffeic acid presented low cytotoxicity, with an IC50 of 327 µM. DOX presented an IC50 of 0.543 µM and the association of DOX (1 µM) with caffeic acid did not affect DOX cytotoxicity at concentrations below 100 µM. Conversely, higher CA concentrations in association with DOX showed that CA modulated DOX, decreasing its antitumor activity. The evaluation of the antioxidant activity of CA revealed a significant antioxidant activity, with EC50 of 47.30 µg/ml (95% CI, 33.77 -37.01), with no statistical differences in relation to Vitamin C (EC50 of 50.16 µg/ml).

Conclusões

Caffeic acid at the concentrations tested did not show significant toxicity or cytotoxicity in the tests evaluated and its association with Doxorubicin may have beneficial effects when in low concentrations.

Financiador do resumo

CNPq

Palavras Chave

àcido cafeico; Toxicogenética; Citotoxicidade