Protective effect of grapefruit juice on the teratogenic and genotoxic damage induced by cadmium in mice.

In the present study, we injected pregnant mice at Day 7 of gestation with cadmium chloride (CC) (1.5 mg/kg) intraperitoneally and determined its effect on the frequency of fetal malformations at Day 17 of pregnancy. On the same day, we also determined the level of micronucleated polychromatic erythrocytes (MNPEs) and of micronucleated normochromatic erythrocytes (MNNEs) in blood cells of both the mothers and their fetuses. A significant increase in the number of malformations was found, mainly exencephaly, micrognathia, ablephary, microphthalmia, and clubfoot, as well as a significant increase in the amount of MNPEs and MNNEs. In addition, pregnant mice were administered grapefruit juice (GJ) orally from Days 0 to 17 of the experiment (from 200 to 800 µL/g) to evaluate the potential of the juice in preventing the damage induced by CC. We found a dose-dependent decrease in the number of visceral and skeletal malformations, as well as in the number of MNPEs and MNNEs, in both the mothers and their fetuses. Furthermore, we determined the level of DNA oxidation by measuring levels of the adduct 8-hydroxy-2'-deoxyguanosine, and we found a significant increase in such level induced by CC; in contrast, there was a significant decrease when we added GJ. Therefore, the observed teratogenic and genotoxic protection can probably be related with the antioxidant potential of GJ.

Design, synthesis, and docking of highly hypolipidemic agents: Schizosaccharomyces pombe as a new model for evaluating alpha-asarone-based HMG-CoA reductase inhibitors.

A series of alpha-asarone-based analogues was designed by conducting docking experiments with published crystal structures of human HMG-CoA reductase. Indeed, synthesis and evaluation of this series showed a highly hypocholesterolemic in vivo activity in a murine model, as predicted by previous docking studies. In agreement with this model, the polar groups attached to the benzene ring could play a key role in the enzyme binding and probably also in its biological activity, mimicking the HMG-moiety of the natural substrate. The hypolipidemic action mechanism of these compounds was investigated by developing a simple, efficient, and novel model for determining HMG-CoA reductase inhibition. The partial purification of the enzyme from Schizosaccharomyces pombe allowed for testing of alpha-asarone- and fibrate-based analogues, resulting in positive and significant inhibitory activity.