Under the conditions tested herein, this study has shown that mice treated with grandisin presented, in a dose-dependent manner, a protective effect against cyclophosphamide-induced mutagenicity. This effect could be, at least in part, associated to grandisin bioactivation. These data open new perspectives for further investigation into the toxicology and applied pharmacology of grandisin.

This study investigated the chemoprotective effects of Punica granatum L. (Punicaceae) fruits alcoholic extract (PGE) on mice exposed to hexavalent chromium [Cr(VI)]. Animals were pretreated with PGE (25, 50 or 75 mg/kg/day) for 10 days and subsequently exposed to a sub-lethal dose of Cr(VI) (30 mg/kg). The frequency of micronucleated polychromatic erythrocytes in the bone marrow was investigated and the Cr(VI) levels were measured in the kidneys, liver and plasm. For the survival analysis, mice were previously treated with PGE for 10 days and exposed to a single lethal dose of Cr(VI) (50 mg/kg). Exposure to a sub-lethal dose of Cr(VI) induced a significant increase in the frequency of micronucleated cells. However, the prophylactic treatment with PGE led to a reduction of 44.5% (25 mg/kg), 86.3% (50 mg/kg) and 64.2% (75 mg/kg) in the incidence of micronuclei. In addition, the 50 mg/kg dose of PGE produced a higher chemoprotective effect, since the survival rate was 90%, when compared to that of the non-treated group. In these animals, reduced amounts of chromium were detected in the biological materials, in comparison with the other groups. Taken together, the results demonstrated that PGE exerts a protective effect against Cr(VI)-induced genotoxicity. Uniterms INTRODUCTIONChromium occurs naturally in the environment in different oxidation states, where Cr(III) and Cr(VI) are the most prevalent. The hexavalent form is usually linked with oxygen and is a strong oxidizing agent. Studies have shown that Cr(VI) is a mutagenic, carcinogenic and teratogenic agent, which easily penetrates the cell membrane in the form of chromate anion (Barceloux, 1999;Acharya et al., 2006;Nickens et al., 2010;Chang et al., 2011;Okello et al., 2012). Its molecular mechanisms of toxicity are not yet fully known, but it is believed that the intracellular increase in the production of reactive oxygen species (ROS) is probably a key factor in inducing cell damage (Ye et al., 1999;Wu et al., 2012). These reactive species can cause damage to macromolecules such as DNA, proteins and lipids, thereby inhibiting their functions (Valko et al., 2007;Yan et al., 2012) and may even trigger apoptotic cell death (Liu, Chen, 2006;Liu et al., 2008).Cr(VI) has been widely used in metallurgical, refractory and chemical industries. It has been considered a potent occupational carcinogen among workers involved in electrodeposition, metal finishes/welding, wood preservatives, organic synthesis procedures and in leather tanning (Barceloux, 1999;Shrivastava et al., 2002;Acharya et al., 2006;Nickens et al., 2010). In such activities occupational exposure to Cr(VI)-contaminated dust and aerosols occurs predominantly through inhalation or skin contact (Zagrodzki et al., 2007). Non-occupational exposure to Cr(VI) can also occur through cigarette smoke, automobile emissions and the inappropriate disposal of chromium-containing waste in the environment (O'Brien et al., 2003;Russo et al., 2005).The literature has shown that the administration of antioxidant agents ...