Efeito quimiopreventivo da Beta-ionona na hepatocarcinogênese associada à fibrose hepática / Chemopreventive effect of Beta-ionone in hepatocarcinogenesis associated with hepatic fibrosis

O carcinoma hepatocelular (HCC) é a neoplasia primária mais frequente que acomete o fígado, a quarta principal causa de morte relacionada ao câncer e apresenta mau prognóstico. A fibrose hepática está presente em grande parte dos casos de HCC e é um dos principais fatores de risco para esta afecção. Segundo estudos prévios do grupo, a ß-ionona (BI), presente em uvas e aromatizantes de vinho, apresenta potencial quimiopreventivo na hepatocarcinogênese principalmente por reduzir o número e tamanho de lesão pré neoplásica (LPN) e inibir a proliferação celular. No entanto, até o presente não foram identificados na literatura estudos que investigaram o efeito deste isoprenóide no processo fibrótico e na hepatocarcinogênese a ele associada. Desta forma, este estudo pretendeu investigar o potencial efeito quimiopreventivo da BI na hepatocarcinogênese associada à fibrose hepática. Para tanto, ratos machos Wistar foram tratados com óleo de milho (OM) [0,25 ml / 100 g de peso corporal (p.c.); Grupo de OM] ou BI (16mg / 100g p.c.; Grupo BI) durante 18 semanas. A partir da 2ª semana, todos os animais receberam uma dose intraperitoneal de dietilnitrosamina (DEN - 50 mg / Kg p.c.) uma vez por semana até a 16ª semana. Os animais foram eutanasiados em diferentes períodos do protocolo experimental: na 10a semana (grupos OMP1 e BIP1), na 14a semana (grupos OMP2 e BIP2) e na 18ª semana (grupos OMP3 e BIP3). O isoprenóide demonstrou, de maneira inédita na literatura, inibir o desenvolvimento da fibrose hepática em diferentes estágios da hepatocarcinogênese (pontos 1, 2 e 3) por reduzir (p < 0,05) a porcentagem de área marcada para picrosirius. Além disso, BI reduziu a porcentagem de área positiva para α- SMA (p < 0,05) e as concentrações de hidroxiprolina (p < 0,05) no ponto 2. Foi observada ação quimiopreventiva da BI nas fases iniciais da hepatocarcinogênese (pontos 1 e 2) mesmo em modelo associada a fibrose por reduzir (p < 0,05) o número e porcentagem de área do corte ocupada por LPN GSTP positivas. Este efeito não foi observado em fase mais avançada da hepatocarcinogênese (ponto 3). Corroborando este dado não foram observadas diferenças em relação ao número de tumores (p>=0,05) avaliados por imageamento e por análise histopatológica. No entanto, quando comparados ao seu controle (OMP3), os animais do grupo BIP3 apresentaram menor mortalidade e menor incidência (p < 0,05) de HCC high, considerado um tipo mais agressivo de HCC, sugerindo que este composto possa atuar na agressividade das células tumorais. O grupo BIP2 demonstrou ainda menor proliferação celular (p < 0,05) quando comparado ao grupo OMP2. Assim foram avaliadas as vias de proliferação celular PI3K/AKT e MAPK/ERK, bem como as proteínas p21 e p53, relacionadas a progressão do ciclo celular. Não foram observadas(p≥0,05) alterações nestas vias por parte do isoprenóide. O presente estudo demonstrou ação protetora da BI no desenvolvimento de fibrose, bem como na hepatocarcinogênese a ela associada. Contudo, são necessárias análises complementares para elucidar mecanismos pelos quais a BI atua na carcinigênese hepática associada à fibrose

Hepatocellular carcinoma (HCC) is the primary liver cancer, the fourth leading cause of death related to cancer and presents a poor prognosis. Hepatic fibrosis is present in most cases of HCC and represents one of the main risk factors for this condition. According to previous studies of the group, ß-ionone (BI), present in grapes and wine flavorings, has a potential chemopreventive in hepatocarcinogenesis mainly by reducing the number and size of preneoplastic lesions (LPN) and inhibiting cell proliferation. However, to date, no studies have been identified in the literature that investigated the effect of this isoprenoid on the fibrotic process and in its association with hepatocarcinogenesis. Thus, this study aimed to investigate the potential chemopreventive effect of BI in hepatocarcinogenesis associated with hepatic fibrosis. Male Wistar rats were treated with corn oil (OM) [0.25 ml / 100 g body weight (b.w.); OM] or BI group (16mg / 100g b.w; BI group) for 18 weeks. From week 2, all animals received an intraperitoneal dose of diethylnitrosamine (DEN - 50 mg / kg b.w.) once in a week until week 16. The animals were euthanized at different periods of the experimental protocol: at week 10 (groups OMP1 and BIP1), at week 14 (groups OMP2 and BIP2) and week 18 (groups OMP3 and BIP3). The isoprenoid, for the first time in the literature, shown to inhibit the development of liver fibrosis at different stages of hepatocarcinogenesis (points 1, 2 and 3) by reducing (p <0.05) the percentage of the area labeled for picrosirius. Also, BI reduced the percentage of α-SMA positive area (p <0.05) and hydroxyproline concentrations (p <0.05) at point 2. BI chemopreventive action was observed in the early stages of hepatocarcinogenesis (point 1 and 2) even in a model associated with fibrosis for reducing (p <0.05) the number and percentage of the liver section area occupied by GSTP positive LPN. This effect was not observed at a later stage of hepatocarcinogenesis (point 3). Corroborating this data, no differences were observed regarding the number of tumors (p>=0.05) evaluated by imaging and histopathological analysis. However, when compared to its control (OMP3), animals from the BIP3 group had lower mortality and lower incidence (p<0.05) of HCC high, considered a more aggressive type of HCC, suggesting that this compound may act in aggressiveness of tumor cells. The BIP2 group also showed lower cell proliferation (p <0.05) when compared to the OMP2 group. Thus, PI3K / AKT and MAPK / ERK cell proliferation pathways were evaluated, as well as p21 and p53 proteins, related to cell cycle progression. No changes were observed in these pathways by the isoprenoid (p≥0.05). The present study demonstrated the protective action of BI in the development of fibrosis, as well as its association with hepatocarcinogenesis. However, further analysis is needed to elucidate mechanisms by which BI acts on fibrosis-associated liver carcinogenesis

Efficacy of geraniol but not of β-ionone or their combination for the chemoprevention of rat colon carcinogenesis

β-ionone (βI), a cyclic isoprenoid, and geraniol (GO), an acyclic monoterpene, represent a promising class of dietary chemopreventive agents against cancer, whose combination could result in synergistic anticarcinogenic effects. The chemopreventive activities of βI and GO were evaluated individually or in combination during colon carcinogenesis induced by dimethylhydrazine in 48 3-week-old male Wistar rats (12 per group) weighing 40-50 g. Animals were treated for 9 consecutive weeks with βI (16 mg/100 g body weight), GO (25 mg/100 g body weight), βI combined with GO or corn oil (control). Number of total aberrant crypt foci (ACF) and of ACF ≥4 crypts in the distal colon was significantly lower in the GO group (66 ± 13 and 9 ± 2, respectively) compared to control (102 ± 9 and 17 ± 3) and without differences in the βI (91 ± 11 and 14 ± 3) and βI+GO groups (96 ± 5 and 19 ± 2). Apoptosis level, identified by classical apoptosis morphological criteria, in the distal colon was significantly higher in the GO group (1.64 ± 0.06 apoptotic cells/mm²) compared to control (0.91 ± 0.07 apoptotic cells/mm²). The GO group presented a 0.7-fold reduction in Bcl-2 protein expression (Western blot) compared to control. Colonic mucosa concentrations of βI and GO (gas chromatography/mass spectrometry) were higher in the βI and GO groups, respectively, compared to the control and βI+GO groups. Therefore, GO, but not βI, represents a potential chemopreventive agent in colon carcrvpdate=20110329inogenesis. Surprisingly, the combination of isoprenoids does not represent an efficient chemopreventive strategy.

A short review of the anthelmintic role of mirazid / Breve revisão sobre a ação anti-helmíntica do mirazid

Mirazid® is a patented preparation from a plant that had been used in folk medicine since ancient Egyptians (Myrrh). It was registered in Egypt for the treatment of schistosomiasis and fascioliasis. Over 32 independent studies for efficacy of Mirazid had been reviewed and their results analyzed. The majority of these studies reported higher than 90 percent cure rates, that even higher in mixed than single trematodal infections in humans and in farm animals. Only two groups of investigators reported lower cure rates as they used lower doses and estimated cure rates at a shorter period from treatment than recommended by innovators.

Mirazid® é um produto patenteado preparado a partir de planta usada na medicina popular desde o Egito antigo conhecida como Mirra. Está registrada no Egito para o tratamento da esquistossomose e da fasciolíase. Foram revistos 32 estudos independentes sobre a eficácia do mirazid e seus resultados analisados. A maioria destes estudos reporta mais de 90 por cento de índice de cura, tanto em infecções mistas por trematódeos em humanos como em animais rurais. Apenas dois grupos de investigadores tiveram baixos índices de cura, mas usaram baixas doses e períodos curtos de tratamento, diferente do recomendado pelos precursores.

The efficacy of a herbal-based toothpaste in the control of plaque and gingivitis: A clinico-biochemical study.

Objective: A double-blinded controlled clinical trial with parallel groups was designed to investigate the effectiveness of a herbal-based toothpaste in the control of plaque and gingivitis as compared with a conventional dentifrice. The efficacy of Colgate Herbal over Colgate tooth paste was assessed in this study. Materials and Methods: Thirty subjects with gingivitis participated in the study. All participants had at least 20 natural teeth with no probing depths greater than 3 mm and a plaque index score of 2 or more at baseline. At baseline, the clinical parameters like gingival index, plaque index and salivary pH were estimated. Paired t-test was used to compare the difference within the groups and unpaired t-test was used to compare the difference between the groups at baseline and on the 30 th day. Results: At the end of the study, there were statistically significant reductions in the gingival index and the plaque index scores within the test group. However, there were no statistically significant differences between the test and the control groups. The salivary pH changes were not statistically significant in the test group but were displaced more toward the acidic range in the control group. Conclusion: It was however concluded that the herbal-based toothpaste was as effective as the conventionally formulated dentifrice in the control of plaque and gingivitis.

Efeito do tratamento in vitro e in vivo do monoterpeno álcool perílico no crescimento e controle da expressão gênica no glioma de alto grau

A pesquisa para o desenvolvimento de novas drogas quimioterápicas, tem se baseado nas propriedades dos produtos de origem natural. Estudos experimentais em animais indicam que o álcool perílico (AP), um monoterpeno originalmente isolado dos óleos essenciais de várias plantas é capaz de causar a regressão de diferentes tipos de tumores. O tratamento clássico preconizado para os astrocitomas anaplásicos e glioblastoma multiforme consiste de: ressecção cirúrgica, radioterapia e/ou quimioterapia e raramente apresentam efeito curativo. O presente trabalho teve como objetivo analisar o efeito do AP na proliferação, na alteração da morfologia, na síntese de proteínas e migração celular de diferentes linhagens de glioblastoma murino e humano. Foram utilizados modelos in vitro de cultivo de células e ensaios in vivo de migração celular. O tratamento in vitro com o AP nas concentrações v/v de 0,003%, 0,02%, 0,03%, 0,3%, 3% e 30% nas linhagens de glioblastoma C6 de murinos e linhagens A 172 e U87MG de glioblastoma humano, mostrou que mesmo nas concentrações (v/v) mais baixas (0,03% e 0,3%) o AP promove a inibição da proliferação celular e da síntese de proteínas. O tratamento in vitro com o AP a 0,3% v/v causou após 15 minutos perda da permeabilidade celular e mais tardiamente, 50 minutos, alterações acentuadas na citoarquitetura das linhagens C6, U87MG e A172. Nos ensaios in vivo com ovos embrionados, o tratamento com o AP nas concentrações v/v 0,3% e 0,03% causou efeito inibitório na migração celular da linhagem C6. Os resultados sugerem uma eficácia quimioterápica do AP na citotoxidade e na inibição da migração celular de linhagens de glioblastoma murino e humano

The search for new chemotherapeutic drugs has increased, especially for those that have a natural origin. Perillyl alcohol (POH), is a naturally occurring monoterpene, found in the essential oils of citrus fruits and other plants, with pronounced chemotherapeutic activity and minimal toxicity in preclinical studies. Standard treatment of anaplastic gliomas and glioblastoma multiforme consisting of surgical resection, radiation therapy and/or chemotherapy is rarely curative. This work aimed to evaluate in vitro and in vivo effects of POH treatment, cell proliferation, changes in morphology, protein synthesis, and migration of distinct lineage of glioblastoma cells. It was chosen in vitro culture systems and in vivo assays for assessing cellular migration. In vitro treatment of POH at concentrations of (v/v) 0.003%, 0.02%, 0.03%, 0.3%, 3% and 30%, consistently inhibited proliferation of murine C6 and human A172 and U87MG of glioblastoma cells. In vitro treatment of POH at low concentrations 0.03% v/v and 0.3% v/v also produced marked changes in cell morphology and inhibited protein synthesis. Likewise in vitro assays with 0.3% v/v POH treatment for 15 minutes, initially caused marked alteration in membrane permeability and later (50 minutes) drastic changes in the cytoarchitecture of C6, U87MG and A172 cells. Furthermore, previous in vitro treatment of glioblastoma cells with 0.3% v/v and 0.03% v/v POH showed inhibition of cell migration and anti-metastatic activity in the in vivo model of the chick embryo with C6 cell line. Such results indicate the chemotherapeutic action of POH by promoting cytotoxicity and arresting migration of murine and human glioblastoma cell lines