Copalic (CA) and kaurenoic (KA) acids are the main diterpenes found in the oleoresin extracted from the copaiba tree (Copaifera sp). This study aimed to characterize the metabolism of CA and KA in rat and human liver microsomes using liquid chromatography with tandem mass spectrometry (LC-MS/MS). The in vitro assays showed deviations from the Michaelian kinetics in the metabolism of CA and KA. Putative metabolites of CA and KA were characterized by LC-MS/MS using electrospray ionization (ESI) with time of flight (LC-ESI-TOF) and ion-trap (LC-ESI-IT) systems and identified as a CA isomer and 16,17-dihydroxy-kaurenoic acid, respectively. CA and KA are subject to extensive metabolism with each passage through the liver with extraction ratios (E) estimated as 0.97 and 0.99, respectively. In conclusion, the kinetic parameters and metabolites described here might support drug development and the traditional use.

Abstract The α-tomatine is a steroidal glycoalkaloid found in immature tomatoes (Lycopersicon esculentum) that has important biological functions including the inhibition of cancer cell growth and preventing metastasis. This study aimed to evaluate the effects of α-tomatine on cytotoxicity, cellular proliferation, apoptosis, and mRNA expression of APC, CCNA2, β-catenin, CASP9, BAK, BAX and BCL-XL in colorectal adenocarcinoma cell line HT-29. HT29 cells were treated with three concentrations of α-tomatine (0.1, 1 and 10 µg/mL), although only the 1 µg/mL concentration of α-tomatine was used to evaluate genetic expression patterns by real time-PCR. Results showed that α-tomatine was cytotoxic only at the 10 µg/mL concentration. Cell proliferation was significantly inhibited after the first 24 hours of treatment only with concentrations of 10 µg/mL. In contrast, there were no significant differences in apoptosis for any treatment. In the gene expression studies, only APC expression was significantly altered by α-tomatine treatment. In conclusion, α-tomatine has antiproliferative activity in the first 24h of treatment, does not induce apoptosis in this cell line and causes disruption of cell membranes, thereby increasing the expression of APC gene related to cell cycle.

Resumo A análise integrada da paisagem apresenta-se como instrumento potencial em estudos de planejamento ambiental, dos quais as Unidades de Conservação são um adequado contexto para a sua aplicação. A seleção do Parque Nacional da Serra da Canastra (PNSC) como lócus de estudo advém da relevância do seu quadro ambiental em escala regional e nacional e, sobretudo, do predomínio de investigações de temáticas ou recortes espaciais específicos. Nesse sentido, este estudo busca contribuir para a análise do PNSC em toda sua extensão e complexidade, a partir da elaboração de proposta de compartimentação regional que contempla as características e relações que se verificam entre unidades espaciais que guardam notória homogeneidade. O conceito de organização estrutural vertical e horizontal foi utilizado na elaboração de nove unidades de paisagem e de uma seção regional que, em conjunto, permitiram a compreensão e análise das inter-relações entre os elementos nas unidades propostas. As unidades foram divididas nos grupos (i) planaltos (ii) depressões e, devido ao forte condicionamento que a litoestrutura e, por conseguinte, as formas de relevo, exerce na evolução da paisagem da região. Somados à análise do uso do terreno, esses foram os principais elementos que fundamentaram a compartimentação e a compreensão da organização estrutural da região.

Abstract The integrated landscape analysis is a potential tool in environmental planning studies and the protected areas are a suitable context for your application. The selection of the Serra da Canastra National Park (PNSC) as study locus derives from the importance of its environmental framework at the regional and national scale and especially the predominance of individual themes or investigations in specific areas. Thus, this study aims to contribute to the analysis of PNSC throughout its length and complexity, from the elaboration of proposed regional subdivision that includes the characteristics and relationships that exist between spatial units that keep striking homogeneity. The concept of vertical and horizontal structural organization was used in the preparation nine landscape units and a regional section that together allowed the understanding and analysis of the interrelations between the elements in the units proposed. The units were divided in two groups (i) plateaus and (ii) lowlands, due to the strong conditioning of the lithology and structure, and therefore relief, exerts the evolution of the landscape of the area. Added to the analysis of land use, these were the main factors which led to compartmentalization and understanding of the structural organization of landscape of the region.

ABSTRACT The study evaluated the effects of brown flaxseed supplementation in natura on the prevention of DNA damage induced by 1,2-dimethylhydrazine (DMH) in vivo. The experimental groups were Negative and Positive Controls and the protocols of Pre-treatment, Simultaneous, Post-treatment, Pre+continuous in relation to the supplementation of brown flaxseed and administration with carcinogenic compound. The results showed that brown flaxseed supplementation does not cause genomic and genetic damage. In addition, brown flaxseed showed a chemopreventive food that reduced the damages assessed by the comet assay up to 94.07x and the damages assessed by the micronucleus assay up to 91.88x. Brown flaxseed supplementation also increased the frequency of monocytes and lymphocytes indicating immunological improvements. Thus, brown flaxseed supplementation is considered safe and reduces the frequency of DNA damage that can lead to tumors. Therefore, if these events are confirmed in humans, flaxseed will have reinforced its indication as a functional chemopreventive food in the prevention of cancer.

Abstract Cardanol is an effective antioxidant and is a compound with antimutagenic and antitumoral activity. Here, we evaluated the genotoxic and mutagenic potential of saturated side chain cardanol and its effects in combination with cyclophosphamide in preventing DNA damage, apoptosis, and immunomodulation. Swiss mice were treated with cardanol (2.5, 5 and 10 mg/kg) alone or in combination with cyclophosphamide (100 mg/kg). The results showed that cardanol is an effective chemopreventive compound, with damage reduction percentages that ranged from 18.9 to 31.76% in the comet assay and from 45 to 97% in the micronucleus assay. Moreover, cardanol has the ability to reduce the frequency of apoptosis induced by cyclophosphamide. The compound did not show immunomodulatory activity. A final interpretation of the data showed that, despite its chemoprotective capacity, cardanol has a tendency to induce DNA damage. Hence, caution is needed if this compound is used as a chemopreventive agent. Also, this compound is likely not suitable as an adjuvant in chemotherapy treatments that use cyclophosphamide.

Inflammatory and genetic alterations are related to the development of chronic diseases such as cancer. Schinus terebinthifolius Raddi, Anacardiaceae, is used in folk medicine to treat inflammation, wounds and tumors. This study evaluated the anti-inflammatory, immunomodulatory, chemopreventive, and wound healing potentials of the methanolic extract from the leaves of Schinus terebinthifolius. The chemical composition of the extract was characterized using preliminary analytical LC methods. The results showed that the anti-inflammatory activity of the methanolic extract was similar to that of dexamethasone for edema reduction. Also, it inhibited the leukocyte migration into the air pouch and decreased plasma extravasation. In addition, the methanolic extract showed a healing action similar to that observed with collagenase. The methanolic extract is not genotoxic nor mutagenic, and in contrast it has chemopreventive activity, which elicits a high percentage of damage reduction by comet and micronucleus assay, preferably by bioantimutagenic action. The methanolic extract induced apoptosis and enhanced splenic phagocytosis in animals treated with cyclophosphamide. The methanolic extract contents, resolved by LC, include phenolic acid and flavonoids. Our results suggest a therapeutic potential for the methanolic extract.

A presente pesquisa teve por objetivo avaliar a capacidade quimiopreventiva da fenilalanina. Utilizou-se um lote de fêmeas prenhes e não prenhes divididas nos seguintes grupos experimentais: G1, PBS (0,1 mL/kg p.c.); G2, ciclofosfamida (35 mg/kg p.c.-i.p.); G3, fenilalanina (150 mg/kg p.c.-v.o.) e G4, fenilalanina (300 mg/kg p.c.-v.o.) e G5 (150 mg/kg p.c. de fenilalanina e 35 mg/kg de ciclofosfamida); G6, (300 mg/kg p.c. de fenilalanina e 35 mg/kg de ciclofosfamida). As coletas de sangue periférico foram realizadas em T0, antes da administração de qualquer substância teste e/ou veículos, e igualmente em T24 e T48, onde as coletas foram realizadas respectivamente 24 e 48 h após a administração da ciclofosfamida. Em uma análise geral verificou-se que, para o grupo de fêmeas não prenhes, a avaliação da antimutagenicidade demonstrou porcentagens de redução de danos de 57,24% e 31,64% para G5 e G6, respectivamente, em T24, e 29,32% e 24,13% para G5 e G6, respectivamente, em T48. Nos animais prenhes a antimutagenicidade de 24 h demonstrou eficiência quimiopreventiva apenas para a menor dose (G5) e as porcentagens de redução de danos foram de 43,25% em G5 e 18,47% em G6. No momento T48 as porcentagens de redução de danos foram de 44,67% e 37,76% para G5 e G6, respectivamente.

This study aimed to evaluate the quimiopreventive ability of phenylalanine. We used pregnant and non-pregnant female mice divided into the following groups: G1-PBS, (0.1 mL/kg b.w); G2, cyclophosphamide (35 mg/kg p.c.-i.p.); G3 and G4, phenylalanine (150 and 300 mg/kg b.w respectively-v.o.) and G5 and G6, association between the two doses of phenylalanine and cyclophosphamide, respectively. The peripheral blood samples were taken at T0, before the administration of any drug test and / or vehicles, also at T24 and T48 where the collections were made 24 and 48 h after administration of cyclophosphamide, respectively. A general analysis has found that, for the group of non-pregnant female, the antimutagenic evaluation showed reduction percentages of damage of 57.24% and 31.64% for G5 and G6, respectively, at T24, and 29.32% and 24.13% for G5 and G6, respectively, at T48. Antimutagenic pregnant animals in the 24 h quimiopreventive efficiency shown only for the lower dose (G5) and the percentages of reduction were 43.25% in G5 and G6 at 18.47%. At T48 the harm-reduction percentages were 44.67% and 37.76% for G5 and G6, respectively.

A presente pesquisa avaliou a ação mutagênica e antimutagênica de um biopolímero de glucose extraído da Agrobacterium radiobacter (Biopolímero de Agrobacterium radiobacter). O experimento foi realizado com camundongos Swiss machos divididos em oito grupos. O tratamento com o biopolímero foi realizado por gavage em dose única concomitante a uma dose de solução tampão fosfato nos grupos de avaliação da mutagenicidade, ou ao agente indutor de danos no DNA, ciclofosfamida, na concentração de 50 mg/kg (peso corpóreo - p.c.), nos grupos de avaliação da antimutagenicidade. Utilizou-se o teste de micronúcleo em sangue periférico e a coleta de sangue foi realizada 24 e 48 h após a aplicação das substâncias-teste. A análise estatística demonstrou que o biopolímero não possui atividade mutagênica e que é efetivo em prevenir danos no DNA. As porcentagens de redução de danos nos grupos de antimutagenicidade foram de 83,9%, 89,1% e 103,1% em 24 h e 101,24%, 98,14% e 120,64% em 48 h para as doses de 75, 150 e 300mg/kg (p.c.), respectivamente. A alta porcentagem de redução de danos associada à ausência de efeitos mutagênicos indica, além da atividade quimioprotetora, a possibilidade do biopolímero ser um alimento funcional candidato à utilização como co-adjuvante na quimioterapia para prevenir efeitos colaterais.

This study evaluated the mutagenic and ant mutagenic action of a biopolymer of glucose extracted from Agrobacterium radiobacter (Biopolymer of Agrobacterium radiobacter). The experiment was conducted with Swiss male mice divided into eight groups. Treatment with the biopolymer was performed in a single dose by gavage at a dose of concomitant phosphate buffer groups in the evaluation of mutagenicity, or the agent of inducing DNA damage, cyclophosphamide, the concentration of 50 mg/kg (body weight --b.w.), in groups of assessment ant mutagenic. We used the micronucleus test in peripheral blood. The blood sample was held 24 and 48 h after application of the test substances. Statistical analysis showed that the biopolymer has no mutagenic activity and it is effective in preventing damage to DNA. The percentages of damage reduction in groups of ant mutagenic were 83.9%, 89.1% and 103.1% in 24 h and 101.24%, 98.14% and 120.64% at doses of 48 to 75, 150 and 300 mg/kg (b.w.) respectively. The high percentage of damage reduction associated with the absence of mutagenic effects indicates the possibility of biopolymer chemoprotection action. It can also be considered a functional food candidate to be used as co-adjuvant chemotherapy to prevent side effects.