Obesity, classified as an epidemic by the WHO, is a disease that continues to grow worldwide. Obesity results from abnormal or excessive accumulation of fat and usually leads to the development of other associated diseases, such as type 2 diabetes, hypertension, cancer, cardiovascular diseases, among others. In vitro and in vivo models have been crucial for studying the underlying mechanisms of obesity, discovering new therapeutic targets, and developing and validating new pharmacological therapies against obesity. Preclinical animal models of obesity comprise a variety of species: invertebrates, fishes, and mammals. However, small rodents are the most widely used due to their cost-effectiveness, physiology, and easy genetic manipulation. The induction of obesity in rats or mice can be achieved by the occurrence of spontaneous single-gene mutations or polygenic mutations, by genetic modifications, by surgical or chemical induction, and by ingestion of hypercaloric diets. In this review, we describe some of the most commonly used murine models in obesity research.
Some diet profiles are associated with the risk of developing cancer; however, some nutrients show protective effects. Porphyra umbilicalis is widely consumed, having a balanced nutritional profile; however, its potential for cancer chemoprevention still needs comprehensive studies. In this study, we incorporated P. umbilicalis into the diet of mice transgenic for the human papillomavirus type 16 (HPV16), which spontaneously develop pre-malignant and malignant lesions, and determined whether this seaweed was able to block lesion development. Forty-four 20-week-old HPV+/− and HPV−/− mice were fed either a base diet or a diet supplemented with 10% seaweed. At the end of the study, skin samples were examined to classify HPV16-induced lesions. The liver was also screened for potential toxic effects of the seaweed. Blood was used to study toxicological parameters and to perform comet and micronucleus genotoxicity tests. P. umbilicalis significantly reduced the incidence of pre-malignant dysplastic lesions, completely abrogating them in the chest skin. These results suggest that P. umbilicalis dietary supplementation has the potential to block the development of pre-malignant skin lesions and indicate its antigenotoxic activity against HPV-induced DNA damage. Further studies are needed to establish the seaweed as a functional food and clarify the mechanisms whereby this seaweed blocks multistep carcinogenesis induced by HPV.
Different types of tumors often present an overexpression of cyclooxygenase-2. The aim of this study was to evaluate the effects of parecoxib (NSAID, cyclooxygenase-2 selective inhibitor) in the behavior of the human osteosarcoma MG-63 cell line, concerning several biological features. Cells were exposed to several concentrations of parecoxib for 48 hours. Cell viability/proliferation, cyclooxygenase-2 expression, morphologic alterations, membrane integrity, cell cycle evaluation, cell death and genotoxicity were evaluated. When compared with untreated cells, parecoxib led to a marked decrease in cell viability/proliferation, in COX-2 expression and changes in cell morphology, in a concentration-dependent manner. Cell recuperation was observed after incubation with drug-free medium. Parecoxib exposure increased lactate dehydrogenase release, an arrest of the cell cycle at S-phase and G2/M-phase, as well as growth of the sub-G0/G1-fraction and increased DNA damage. Parecoxib led to a slight increase of necrosis regulated cell death in treated cells, and an increase of autophagic vacuoles, in a concentration-dependent manner. In this study, parecoxib showed antitumor effects in the MG-63 human osteosarcoma cells. The potential mechanism was inhibiting cell proliferation and promoting necrosis. These results further suggested that parecoxib might be a potential candidate for in-vivo studies.
Obesity is a disease whose incidence has increased over the last few decades. Despite being a multifactorial disease, obesity results essentially from excessive intake of high-calorie foods associated with low physical activity. The demand for a pharmacological therapy using natural compounds as an alternative to synthetic drugs has increased. Natural compounds may have few adverse effects and high economic impact, as most of them can be extracted from underexploited plant species and food by-products. To test the potential anti-obesogenic effects of new natural substances, the use of preclinical animal models of obesity has been an important tool, among which rat and mouse models are the most used. Some animal models are monogenic, such as the db/db mice, ob/ob mice, Zucker fatty rat and Otsuka Long-Evans Tokushima fatty rat. There are also available chemical models using the neurotoxin monosodium glutamate that induces lesions in the ventromedial hypothalamus nucleus, resulting in the development of obesity. However, the most widely used are the obesity models induced by high-fat diets. The aim of this review was to compile detail studies on the anti-obesity effects of natural compounds or their derivatives on rodent models of obesity as well as a critical analysis of the data.
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