Cancer is the first cause of death in developed countries and the second in developing countries. Concerning the most frequent worldwide-diagnosed cancer, primary liver cancer represents approximately 4% of all new cancer cases diagnosed globally. However, among primary liver cancer, hepatocellular carcinoma is by far the most common histological subtype. Notwithstanding the health promotion and disease prevention campaigns, more than half a million new hepatocellular carcinoma cases are reported yearly, being estimated to growth continuously until 2020. Taking this scenario under consideration and the fact that some aspects concerning hepatocellular carcinoma evolution and metastasize process are still unknown, animal models assume a crucial role to understand this disease. The animal models have also provided the opportunity to screen new therapeutic strategies. The present review was supported on research and review papers aiming the complexity and often neglected chemically induced animal models in hepatocarcinogenesis research. Despite the ongoing debate, chemically induced animal models, namely, mice and rat, can provide unique valuable information on the biotransformation mechanisms against xenobiotics and apprehend the deleterious effects on DNA and cell proteins leading to carcinogenic development. In addition, taking under consideration that no model achieves all hepatocellular carcinoma research purposes, criteria to define the "ideal" animal model, depending on the researchers' approach, are also discussed in this review.

The use of chemical compounds benefits society in a number of ways. Pesticides, for instance, enable foodstuffs to be produced in sufficient quantities to satisfy the needs of millions of people, a condition that has led to an increase in levels of life expectancy. Yet, at times, these benefits are offset by certain disadvantages, notably the toxic side effects of the chemical compounds used. Exposure to these compounds can have varying effects, ranging from instant death to a gradual process of chemical carcinogenesis. There are three stages involved in chemical carcinogenesis. These are defined as initiation, promotion and progression. Each of these stages is characterised by morphological and biochemical modifications and result from genetic and/or epigenetic alterations. These genetic modifications include: mutations in genes that control cell proliferation, cell death and DNA repair -i.e. mutations in proto-oncogenes and tumour suppressing genes. The epigenetic factors, also considered as being non-genetic in character, can also contribute to carcinogenesis via epigenetic mechanisms which silence gene expression. The control of responses to carcinogenesis through the application of several chemical, biochemical and biological techniques facilitates the identification of those basic mechanisms involved in neoplasic development. Experimental assays with laboratory animals, epidemiological studies and quick tests enable the identification of carcinogenic compounds, the dissection of many aspects of carcinogenesis, and the establishment of effective strategies to prevent the cancer which results from exposure to chemicals.

Nebivolol protects against renal fibrosis, oxidative stress and endothelial dysfunction better than equivalent doses, in terms of arterial pressure reduction, of atenolol in a hypertensive model of renal damage induced by RMR.

Bearded Capuchin or Black-striped Capuchin monkeys (Sapajus lidibinosus) are New World robust capuchin monkeys widely used in medical research. Few data are available concerning hematological reference values for these species, with no studies available from the Northeast region in Brazil. The aim of this study was to determine the hematological reference values for healthy bearded capuchin monkeys and to analyze the influence of sex and age factors. Blood samples were collected from 50 healthy bearded capuchin monkeys housed in captivity. These were analysed for total erythrocyte, hemoglobin, leukocyte and platelet count, packed cell volume (PCV), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC). When considering the age factor, significant differences were reported for total erythrocyte count, PCV, hemoglobin, total leucocytes, band neutrophils, eosinophils and lymphocytes (higher in juveniles). Significant sex-associated differences were noted for total erythrocyte count, PCV, hemoglobin (higher in males) and number of lymphocytes (higher in females).We have reported for the first time the hematological profile of bearded capuchin monkeys in captivity in the state of Paraíba, Brazil. These results can contribute for a better understanding of the normal physiology of capuchin monkeys, while demonstrating that factors such as sex and age influence hematological parameters should be taken into consideration in the hematological evaluation of this species. RESUMO: Os macacos-prego (Sapajus lidibinosus) são macacos capuchinhos robustos do Novo Mundo amplamente utilizados na pesquisa médica. Poucos dados estão disponíveis sobre valores de referência hematológicos para essas espécies, e não há estudos na região Nordesteno Brasil. O nosso objetivo foi determinar os valores de referência hematológicos para macacos-prego saudáveis e analisar a influência de fatores como o sexo e a idade. Foram coletadas amostras de sangue de 50 macacos-prego saudáveis alojados em cativeiro. Determinaram-se as contagens de eritrócitos, hemoglobina, leucócitos e plaquetas, hematócrito, volume corpuscular médio (MCV), hemoglobina corpuscular média (MCH) e concentração média de hemoglobina corpuscular (MCHC). Foram encontradas diferenças significativas relacionadas à idade para a contagem total de eritrócitos, hematócrito, hemoglobina, leucócitos totais, neutrófilos em banda, eosinófilos e linfócitos (maior em juvenis). Diferenças significativas associadas ao sexo foram observadas para a contagem total de eritrócitos, hematócrito, hemoglobina (maior nos machos) e número de linfócitos (maior nas fêmeas). Relatamos o primeiro perfil hematológico de macacos-prego alojados em cativeiro no estado da Paraíba, Brasil. Estes resultados contribuem para uma melhor compreensão da normal fisiologia dos macacos-prego e demonstram que fatores como sexo e a idade têm influência e devem ser considerados na sua avaliação hematológica. Palavras-chave: Sapajus libidinosus, hematologia, parâm...

Oral gavage is a widely used method for administering substances to animals in pharmacological and toxicological studies. The authors evaluated whether oral gavage causes behavioral indicators of stress, increased mortality rate, alterations in food and water consumption and body weight or histological lesions in CD-1 mice. Gavage was carried out once per d for 5 d per week over 6 consecutive weeks. The mortality rate of mice in this study was 15%. Mice subjected to gavage did not undergo changes in food or water consumption during the study, and their mean body weights and relative organ weights were similar to those of mice in the control group. Serum cortisol levels at the time of euthanasia in mice in both groups were within the normal range. Histopathology showed acute esophagitis and pleurisy, indicative of perforation of the esophagus, in the two mice that died but no abnormalities in the other mice. The results suggest that animal stress and mortality related to oral gavage can be minimized when the procedure is carried out by an experienced technician.

Animal models, namely mice, have been used to study chemically induced carcinogenesis due to their similarity to the histological and genetic features of human patients. Hepatocellular carcinoma (HCC) is a common malignancy with poor clinical outcome. The high incidence of HCC might be related to expo-sure to known risk factors, including carcinogenic compounds, such as N-nitrosamines, which cause DNA damage. N-nitrosamines affect cell mitochondrial metabolism, disturbing the balance between reactive oxygen species (ROS) and antioxidants, causing oxidative stress and DNA damage, potentially leading to carcinogenesis. This work addresses the progressive histological changes in the liver of N-diethylnitrosamine (DEN)-exposed mice and its correlation with oxidative stress.Male ICR mice were randomly divided into five DEN-exposed and five matched control groups. DEN was IP administered, once a week, for eight consecutive weeks.2 Samples were taken 18 h after the last DEN injection (8 weeks post-exposure). The following sampling occurred at weeks 15th, 22nd, 29th and 36th after the first DEN injection. DEN resulted in early toxic lesions and, from week 29 onwards, in progressive proliferative lesions. Between 15 and 29 weeks, DEN-exposed animals showed significant changes in hepatic antioxidant (glutathione, glutathione reductase, and catalase) status (p < 0.05) compared with controls. These results point to an association between increased DEN-induced oxidative stress and the early histopathological alterations, suggesting that DEN disrupted the antioxidant defense mechanism, thereby triggering liver carcinogenesis.

No abstract

The purpose of this study was to determine whether everolimus, a rapamycin derivative, might significantly enhance the cytotoxicity of gemcitabine, an antitumor drug, in two human bladder-cancer cell lines. Human bladder-cancer T24 and 5637 cells were incubated with gemcitabine and everolimus in a range of concentrations either alone or in combination for 72 h. Flow cytometry, comet assay, MTT method and optical microscopy were used to assess cell proliferation, cell cycle, DNA damage, and morphological alterations. Gemcitabine exerted an inhibitory effect on T24 and 5637 cell proliferation, in a concentration-dependent manner. Everolimus significantly reduced proliferation of 5637 bladder cancer cells (IC₃₀) at 1 μM), whereas T24 demonstrated marked resistance to everolimus treatment. A significant antiproliferative effect was obtained combining gemcitabine (100 nM) with everolimus (0.05-2 μM) with an arrest of cell cycle at S phase. Furthermore, an increase in frequency of DNA damage, apoptotic bodies, and apoptotic cells was observed when T24 and 5637 cancer cells were treated simultaneously with both drugs. Data show that in vitro combination produced a more potent antiproliferative effect when compared with single drugs.