Protective effects of the exopolysaccharide Lasiodiplodan against DNA damage and inflammation induced by doxorubicin in rats: Cytogenetic and gene expression assays.

The lasiodiplodan (LS) is a ß-(1→6)-d-glucan produced by the fungus Lasiodiplodia theobromae and some of the biological activities of LS were reported as hypoglycemic, anticoagulant, anti-proliferative and anticancer action; however, its effects on DNA instability and modulation of gene expression are still unclear. Aims of study were investigate the genotoxic effects of lasiodiplodan, and its protective activity against DNA damage induced by doxorubicin (DXR) and its impact on the expression of genes associated with DNA damage and inflammatory response pathways. Therefore, Wistar rats were treated (15 days) orally with LS (5.0; 10 and 20mg/kg bw) alone and in combination with DXR (15mg/kg bw; administrated intraperitoneally on 14th day) as well as their respective controls: distilled water and DXR. Monitoring of DNA damage was assessed by comet and micronucleus (MN) assays and gene expression was evaluated by PCR-Arrays. Treatments with LS alone did not induce disturbances on DNA; when LS was given in combination with DXR, comet and MN formations were reduced to those found in the respective controls. Moreover, LS was able to reduce the disturbances on gene expressions induced by DXR treatment, since the animals that receive LS associated with DXR showed no alteration in the expression of genes related to DNA damage response. Also, DXR induced several up- and down-regulation of several genes associated to inflammatory process, while the animals that received LS+DXR had their gene expression patterns similar to those found in the control group. In conclusion, our results showed that LS did not induce disturbances on DNA stability and significantly reduce the DNA damage and inflammation caused by DXR exposure. In addition, we give further information concerning the molecular mechanisms associated to LS protective effects which seems to be a promising nutraceutical with chemopreventive potential.

Genotoxic action of the sesquiterpene lactone centratherin on mammalian cells in vitro and in vivo.

Centratherin is a sesquiterpene lactone known for its antimicrobial, anti-inflammatory, and trypanocidal activities. The aim of this study was to determine the clastogenic and cytotoxic potential of centratherin in human lymphocytes and in mice. Human lymphocytes in culture were submitted to either continuous treatment or treatment during G(2) phase of the cell cycle. After continuous treatment the 0.2 microg/ml concentration induced a significant increase in total of chromosomal aberrations (CA) and sister chromatid exchange compared to control, and it reduced the mitotic index (MI). In the treatment during G(2) phase, centratherin induced a significant increase in the frequency of CA for all concentrations tested (0.1, 0.3, and 0.5 microg/ml). In the in vivo test system all three concentrations tested in mice (3.3, 6.7, and 13.3 mg/kg b.w.) induced a significant increase in CA compared to the negative control. On the basis of these results, centratherin showed clastogenic and cytotoxic activity on in vitro and in vivo mammalian systems.

Assessment of the cytotoxic and clastogenic activities of the sesquiterpene lactone lynchnopholide in mammalian cells in vitro and in vivo.

Lychnopholide (LNP), a sesquiterpene lactone with antitumor, trypanocidal, and antimicrobial activities, was isolated from Vanillosmopsis erythropappa. The present study was carried out to assess the cytotoxic and clastogenic potential of this new agent in human cultured lymphocytes and Swiss bone marrow cells before the agent was used in medicine. The mitotic index, chromosomal aberrations (CAs), sister chromatid exchanges (SCEs), and proliferation index were investigated. There was no alteration in the number of CAs and SCEs in the continuous in vitro treatment. However, the highest concentration (0.2 microg/ml) of LNP was cytotoxic. LNP (0.1, 0.2, and 0.4 microg/ml) induced a significant increase in CA frequency at the G2 phase in all treated cultures. Only the highest concentration (26.67 mg/kg) caused a significant increase in the total number of CAs in the in vivo investigation. On the basis of these results, LNP had a clastogenic effect on both test systems and a cytotoxic effect in vitro.