Effect on nutritional markers of a model of aberrant crypt foci induced by azoxymethane and sodium dextran sulfate in Sprague Dawley rats.

INTRODUCTION: Introduction: aberrant crypt foci (ACF) are colon preneoplastic lesions that can be used as a tool to study preventive processes for colorectal cancer (CRC). This model consists of initiation induced by azoxymethane (AOM) and promoted by sodium dextran sulfate (DSS), simulating human colonic carcinogenesis in a rat model. There is no direct information on the effects of this process on nutritional markers. Objective: to determine the effect on nutritional markers after the induction of ACF by AOM/DSS in a rat model. Methods: ACF were induced in 24 four-week-old Sprague Dawley male rats by administration of 2 AOM injections (10 mg/kg) and 7 days of 2% DSS in their drinking water. Body weight gain, food and fluid intake, weight of sacrificial organs, nutritional biochemical profiles, liver and kidney toxicity were evaluated. Cell counts in blood were also performed and histological sections evaluated in specific organs. The model was confirmed with identification and counts of ACF. Half of the rats were sacrificed at the sub-chronic stage and the rest at the chronic stage. Results: at the sub-chronic stage, changes in the liver and colon weight, and in the lymphocyte count were observed. For both stages, histopathological damage was observed in liver, kidney and colon, along with alterations in serum glucose levels. Conclusions: the model for proposed ACF can be used at the sub-chronic stage without the need for observation at the chronic stage. More research is needed to determine the mechanism of the observed effects.

INTRODUCCIÓN: Introducción: los focos de criptas aberrantes (ACF) son lesiones preneoplásicas en colon que pueden ser utilizados como herramienta para estudiar procesos preventivos para el cáncer colorectal (CCR). Este modelo consiste en la iniciación inducida por azoximetano (AOM) y promovida por dextrano sulfato sódico (DSS) simulando una carcinogénesis colónica humana en un modelo de rata. No existe información directa de los efectos sobre marcadores nutricios para este proceso. Objetivo: determinar el efecto sobre marcadores nutricios tras la inducción de ACF por AOM/DSS en un modelo de rata. Métodos: se utilizaron veinticuatro ratas machos Sprague Dawley de 4 semanas para la inducción de ACF por administración de 2 inyecciones de AOM (10 mg/kg) y 7 días de DSS al 2% en el agua para beber. Se evaluó la ganancia de peso corporal, el consumo de alimento y de líquidos, el peso de órganos al sacrificio, perfiles bioquímicos nutricios, de toxicidad hepática y renal. Asimismo, se realizaron conteos celulares en sangre y se evaluaron cortes histológicos en órganos específicos. El modelo se confirmó con la identificación y conteos de ACF. Se sacrificó la mitad de las ratas en etapa subcrónica y las demás en etapa crónica. Resultados: en la etapa subcrónica se observaron cambios entre grupos en el peso del hígado y colon, y en el conteo de linfocitos. En ambas etapas se observaron daños histopatológicos en hígado, riñón y colon, así como alteraciones en los niveles de glucosa sérica. Conclusiones: el modelo para ACF propuesto puede ser utilizado en etapa subcrónica sin necesidad de llevarlo a tiempo crónico. Es necesaria más investigación para determinar el mecanismo de los efectos observados.

A novel myokine, secreted protein acidic and rich in cysteine (SPARC), suppresses colon tumorigenesis via regular exercise.

OBJECTIVE: Several epidemiological studies have shown that regular exercise can prevent the onset of colon cancer, although the underlying mechanism is unclear. Myokines are secreted skeletal muscle proteins responsible for some exercise-induced health benefits including metabolic improvement and anti-inflammatory effects in organs. The purpose of this study was to identify new myokines that contribute to the prevention of colon tumorigenesis. METHODS: To identify novel secreted muscle-derived proteins, DNA microarrays were used to compare the transcriptome of muscle tissue in sedentary and exercised young and old mice. The level of circulating secreted protein acidic and rich in cysteine (SPARC) was measured in mice and humans that performed a single bout of exercise. The effect of SPARC on colon tumorigenesis was examined using SPARC-null mice. The secretion and function of SPARC was examined in culture experiments. RESULTS: A single bout of exercise increased the expression and secretion of SPARC in skeletal muscle in both mice and humans. In addition, in an azoxymethane-induced colon cancer mouse model, regular low-intensity exercise significantly reduced the formation of aberrant crypt foci in wild-type mice but not in SPARC-null mice. Furthermore, regular exercise enhanced apoptosis in colon mucosal cells and increased the cleaved forms of caspase-3 and caspase-8 in wild-type mice but not in SPARC-null mice. Culture experiments showed that SPARC secretion from myocytes was induced by cyclic stretch and inhibited proliferation with apoptotic effect of colon cancer cells. CONCLUSIONS: These findings suggest that exercise stimulates SPARC secretion from muscle tissues and that SPARC inhibits colon tumorigenesis by increasing apoptosis.