Segurança do extrato aquoso das sementes de Aleurites moluccana (L.) Willd. em ensaios in vitro e in vivo

Abstract

Plants are popularly used as an alternative to medicines, however, many plant species do not have their elucidated toxicology. The lack of these studies together with the ability of plants to have adverse effects warns of this practice that may endanger the health of their consumers. Aleurites moluccana, belongs to the Euphorbiaceae family and has a seed popularly known as "India nut" which is used as a source of weight loss, however, there are no studies proving the safety of its intake. In this sense, the objective of this work was to evaluate the potential of oral toxicity, cytotoxicity, mutagenicity and genotoxicity in vitro and in vivo assays of aqueous extract of Aleurites moluccana (EASAM) seeds. In the acute oral toxicity test the dose of 2000 mg/kg EASAM was orally administered once to Wistar rats and was observed for 14 days. For short term oral toxicity, comet and micronucleus the animals were treated for 28 days and was established a negative control group, three test groups treated with doses of 100; 50 and 25 mg/kg EASAM and a positive control group treated with cyclophosphamide for the micronucleus assay. In addition, only for short-term oral toxicity was added to a satellite group treated with the 100 mg/kg dose and its negative saline-treated control that was kept under observation for 14 days after the end of the experiment to observe late, persistent or reversible toxic effects. For the Ames test the concentrations of 5000 were used; 1500; 500; 150 and 50 μg/plate against TA97a, TA98, TA 100 and TA 1535 strains with and without metabolic activation and the same concentrations were used for the MTS assay against tumor (Hela and SiHa) and non-tumor (Vero) cells. In the acute oral toxicity test, the EASAM presented at LD50 > 2000 mg/kg and was evaluated as little toxic. In the short-term oral toxicity test, animals receiving doses of 100, 50 and 25 mg/kg of EASAM showed no biochemical, hematological, histopathological alterations and clinical signs of toxicity. In the comet and micronucleus test, the administered doses of EASAM did not cause DNA damage to cells or increase the number of micronucleus in the erythrocytes of animals when compared to the negative control. In addition, the concentrations evaluated of EASAM did not show in vitro mutagenic potential by the Ames test, because the IM < 2. In the cytotoxicity assay, the 5000 μg/plate dose of EASAM at the highest concentration reduced the cell viability of all strains by more than 50%, and at the lowest concentrations maintained the viability of the reduced tumor strains (65 - 95%). According to the results of this work, EASAM at the evaluated conditions and concentrations does not present short term oral toxicity, in vitro and in vivo mutagenic potential and in vivo genotoxic, but demonstrates an antiproliferative potential.