Cristiene Costa Carneiro

Chemopreventive effect and angiogenic activity of punicalagin isolated from leaves of Lafoensia pacari A. St.-Hil.

Punicalagin is the major ellagitannin constituent from leaves of Lafoensia pacari, a Brazilian medicinal plant widely used for the treatment of peptic ulcer and wound healing. Genotoxic, cytotoxic, antigenotoxic, and anticytotoxic effects of punicalagin were assessed using micronucleus (MN) test and comet assay in mice. Due to the extensive use of L. pacari in the wound healing process, we also assessed the angiogenic activity of punicalagin using the chick chorioallantoic membrane (CAM) angiogenic assay. The highest dose of punicalagin (50mg/kg) showed significant cytotoxic effect by MN test and in the co-treatment with cyclophosphamide (CPA), this cytotoxicity was enhanced. Co-treatment, pre-treatment and post-treatment of punicalagin with CPA led to a significant reduction in the number of DNA breaks and in the frequency of CPA-induced MN, indicating antigenotoxic effect. Using the CAM model, punicalagin exhibited angiogenic activity in all doses mainly at the lowest concentration (12.5μg/μL). Therefore, these findings indicate an effective chemopreventive role of punicalagin and a high capacity to induce DNA repair. Also, the angiogenic activity presented by punicalagin in this study could contribute for the processes of tissue repairing and wound healing.

Cytotoxic and Chemopreventive Effects of Gemin D Against Different Mutagens Using In Vitro and In Vivo Assays

BACKGROUND Gemin D (GD) is an ellagitannin found in several plant species rich in phenolic compounds. Its many beneficial properties include antioxidant and antitumoral. OBJECTIVE The present study assessed the genotoxicity, cytotoxicity, antigenotoxicity, and anticytotoxicity of GD by in vitro and in vivo assays. METHOD The Ames mutagenicity assay in Salmonella typhimurium, Micronucleus and Comet tests in mice were used to evaluate the biological activities mentioned above. To assess the GDs protective effects against DNA damage induced by different mutagens we performed co-, pre- and/or post-treatment in these assays. RESULTS There was no genotoxic effect of GD via Ames and Micronucleus tests, but in the Comet assay the highest dose induced DNA damage. This same highest dose presented a significant cytotoxicity in mice. In the antigenotoxicity, GD protected DNA against the action of 4-nitroquinoline-1-oxide and sodium azide by Ames test, and also against the harmful action of cyclophosphamide in pre- and co-treatment by Micronucleus and Comet tests, but it did not protect DNA in post-treatment. Regarding to anticytotoxicity, GD provoked an anticytotoxic effect only during pre-treatment. CONCLUSION Therefore, GD showed relevant antigenotoxic, anticytotoxic and cytotoxic effects, which indicate that it may be a probable candidate for chemoprevention or for the development of new cancer therapies.

Antigenotoxicity protection of Carapa guianensis oil against mitomycin C and cyclophosphamide in mouse bone marrow

The aim of this study was to evaluate the possible protective of C. guianensis oil against MMC and CP, which are direct- and indirect-acting chemical mutagens, using the micronucleus test. Three experiments were performed. First the C. guianensis oil was co-administered to mice at doses of 250, 500 and 1000 mg/kg bw with 4 mg/kg bw MMC or 50 mg/kg bw CP. Second, the mutagenic drug (CP) was administered ip 50 mg/kg bw and after 6 and 12 hours 250 and 500 mg/kg bw of C. guianensis oil were administered. In the last, C. guianensis oil was administrated (250 and 500 mg/kg bw) during five days and after it was administered ip 50 mg/kg bw CP. The results obtained showed that the C. guianensis oil is not cytotoxic neither genotoxic to mouse bone marrow. Regarding the antimutagenic effect, all doses of C. guianensis oil were significantly (p < 0.05) effective in reducing the frequency of micronucleated polychromatic erythrocytes, when compared with MMC or CP alone. Based on these results, our results suggest that the C. guianensis oil shows medicinal potential as an antimutagenic agent, modulating the mutagenicity caused by both direct- and indirect-acting chemical mutagens, in a mammalian model.

Antitumor effectiveness and mechanism of action of Ru(II)/amino acid/diphosphine complexes in the peritoneal carcinomatosis progression:

Peritoneal carcinomatosis is considered as a potentially lethal clinical condition, and the therapeutic options are limited. The antitumor effectiveness of the [Ru(l-Met)(bipy)(dppb)]PF6 (1) and the [Ru(l-Trp)(bipy)(dppb)]PF6 (2) complexes were evaluated in the peritoneal carcinomatosis model, Ehrlich ascites carcinoma–bearing Swiss mice. This is the first study that evaluated the effect of Ru(II)/amino acid complexes for antitumor activity in vivo. Complexes 1 and 2 (2 and 6 mg kg−1) showed tumor growth inhibition ranging from moderate to high. The mean survival time of animal groups treated with complexes 1 and 2 was higher than in the negative and vehicle control groups. The induction of Ehrlich ascites carcinoma in mice led to alterations in hematological and biochemical parameters, and not the treatment with complexes 1 and 2. The treatment of Ehrlich ascites carcinoma–bearing mice with complexes 1 and 2 increased the number of Annexin V positive cells and cleaved caspase-3 levels and induced changes in the cell morphology and in the cell cycle phases by induction of sub-G1 and G0/G1 cell cycle arrest. In addition, these complexes reduce angiogenesis induced by Ehrlich ascites carcinoma cells in chick embryo chorioallantoic membrane model. The treatment with the LAT1 inhibitor decreased the sensitivity of the Ehrlich ascites carcinoma cells to complexes 1 and 2 in vitro—which suggests that the LAT1 could be related to the mechanism of action of amino acid/ruthenium(II) complexes, consequently decreasing the glucose uptake. Therefore, these complexes could be used to reduce tumor growth and increase mean survival time with less toxicity than cisplatin. Besides, these complexes induce apoptosis by combination of different mechanism of action.

Main Serological Markers of Systemic Rheumatic Autoimmune Diseases

Systemic rheumatic autoimmune diseases are complex chronic inflammatory disorders, generally with impairment of joins and systemic manifestations. This study is a literature review about the main serologic markers used in the screening of these illnesses. The assessment of the presence of autoantibodies is an essential component in the initial diagnosis of autoimmune diseases. The production of these antibodies occurs via humoral immune response against self-antigens, and these antibodies are often present in the serum of patients diagnosed with autoimmune illness. Each antibody has a different function and specificity and this is directly associated with clinic manifestations and disease course. The main markers detected in rheumatology have antinuclear, prothrombotic and inflammatory action; therefore depending on the complexity of the illness, several markers can be identified, assisting both in diagnosis and prognosis disease. ---------------------------------------------------------------------------------- Principais marcadores sorologicos de doencas reumaticas autoimunes sistemicas Doencas reumaticas autoimunes sistemicas sao doencas inflamatorias cronicas, complexas, geralmente com comprometimento das articulacoes acompanhado de manifestacoes sistemicas. O presente estudo trata-se de uma revisao bibliografica sobre os principais marcadores sorologicos utilizados no rastreio dessas doencas. A avaliacao da presenca de autoanticorpos constitui parte essencial no diagnostico inicial de doencas autoimunes. A producao desses anticorpos ocorre atraves de resposta imune humoral contra antigenos proprios, e estao frequentemente presentes no soro de pacientes diagnosticados com doenca autoimune. Cada anticorpo tem funcao, e especificidade diferentes, e isso influencia diretamente na manifestacao e curso da doenca. Os principais marcadores detectados em reumatologia tem acao antinuclear, pro-trombotica e inflamatoria, por isso, dependendo da complexidade da doenca, varios marcadores podem ser encontrados, auxiliando tanto no diagnostico quanto no prognostico. ---------------------------------------------------------------------------------- ■ Text in Portuguese

Genotoxic and Cytotoxic Effects of Antiretroviral Combinations in Mice Bone Marrow

Commonly used guidelines for the management of human immunodeficiency virus (HIV) infection (highly active antiretroviral therapy, HAART) include drug combinations such as tenofovir disoproxil fumarate (TDF) + lamivudine (3TC) and combivir [zidovudine (AZT) + 3TC] + efavirenz (EFV). These combinations may enhance the genotoxic effects induced by such drugs individually, since the therapy requires lifelong adherence and the drugs have unknown effects during treatment. Thus, the evaluation of the benefits and risks of HAART is of great importance. In order to assess the cytotoxic and genotoxic potential of three concentrations of each of the antiretroviral combinations TDF + 3TC (800 + 400, 1600 + 800, and 3200 + 1600 mg/kg body weight, BW) and combivir + EFV (200 + 100 + 400, 400 + 200 + 800, and 800 + 400 + 1600 mg/kg BW) after two exposure periods (24 h and 48 h), in the present study the in vivo comet assay (single-cell gel electrophoresis) and the mouse bone marrow micronucleus test were used. Neither TDF + 3TC nor combivir + EFV induced DNA damage at any concentrations tested after 24 h or 48 h using the comet assay. After 24 h, both combinations increased the micronucleus frequency at all concentrations tested. After 48 h, combivir + EFV increased the micronucleated polychromatic erythrocyte (MNPCE) frequency at the two highest concentrations tested. Polychromatic erythrocytes (PCE)/normochromatic erythrocytes (NCE) ratio was high for both combinations, suggesting that they can be mitogenic. Since genotoxicity may be related to carcinogenesis, it is necessary to conduct further studies to verify the long-term mutagenic effects of these drugs.