Evaluation of genotoxic and cytotoxic effects of hydroalcoholic extract of Euphorbia tirucalli (Euphorbiaceae) in cell cultures of human leukocytes.

Euphorbia tirucalli (L.), commonly known as aveloz, has been indiscriminately used in popular medicine to treat various illnesses. However, some components can have devastating consequences. Injury to a cell's genetic material can cause mutations, cancer, and cell death. Our main goal in this work was to evaluate the genotoxic and cytotoxic effects of E. tirucalli extract on human leukocytes. For this purpose, we performed a phytochemical analysis to evaluate the plant's components. In the second step, we treated cultured human leukocytes with different concentrations of the dry extract of the plant and then evaluated the oxidative and genotoxic profiles of these leukocytes. We found that at 1% and 10% concentrations, the aveloz extract acted as a genotoxic agent that could damage DNA and increase oxidative damage. We conclude that despite its popular use, aveloz can act as a genotoxic agent, especially when it contains phorbol ester. Aveloz's indiscriminate use might actually promote tumors and therefore carry a considerable genetic risk for its users.

Structure-based design of δ-lactones for new antifungal drug development: susceptibility, mechanism of action, and toxicity.

Dermatophytes are the etiological agents of cutaneous mycoses, including the prevalent nail infections and athlete's foot. Candida spp. are opportunistic and emerging pathogens, causing superficial to deeper infections related to high mortality rates. As a consequence of prolonged application of antifungal drugs, the treatment failures combined with multidrug-resistance have become a serious problem in clinical practice. Therefore, novel alternative antifungals are required urgently. δ-Lactones have attracted great interest owing to their wide range of biological activity. This article describes the antifungal activity of synthetic δ-lactones against yeasts of the genus Candida spp. and dermatophytes (through the broth microdilution method), discusses the pathways by which the compounds exert this action (toward the fungal cell wall and/or membrane), and evaluates the toxicity to human leukocytes and chorioallantoic membrane (by the hen's egg test-chorioallantoic membrane). Two of the compounds in the series presented broader spectrum of antifungal activity, including against resistant fungal species. The mechanism of action was related to damage in the fungal cell wall and membrane, with specific target action dependent on the type of substituent present in the δ-lactone structure. The damage in the fungal cell was corroborated by electron microscopy images, which evidenced lysed and completely altered cells after in vitro treatment with δ-lactones. Toxicity was dose dependent for the viability of human leukocytes, but none of the compounds was mutagenic, genotoxic, or membrane irritant when evaluated at higher concentrations than MIC. In this way, δ-lactones constitute a class with excellent perspectives regarding their potential applications as antifungals.