Efeitos do uso oral de quercetina na caquexia relacionada ao modelo tumoral murino singênico de melanoma cutâneo

Abstract

The progression of cancer leads some individuals to present a paraneoplastic syndrome known as Cancer-related cachexia (CRC), which is characterized as a systemic pathological state, of progressive physical consumption due to the increase in catabolic activity in skeletal muscle tissues (SMT) and adipose. Quercetin (Querc) is a phytonutrient that exhibits a wide range of modulating effects on altered molecular pathways that are related to the progression of cancer. The study aimed to investigate the effects of Querc on gene expression, body weight, muscle strength and volume, plasma biomarkers, histomorphometric parameters of white adipose tissue (WAT) and SMT, diagnosis of CRC and cancer-related survival (CRS) of C57BL/ 6mice submitted to the murine syngene model of cutaneous melanoma (SCMM) and making a utility model for resistance exercise with rodents. This study was submitted to the ethics committee in research and animal welfare and received assent for its performance (CEB / Unimontes; Nº. 102/2016). B16F10 murine cutaneous melanoma cells were inoculated in the flank of female C57BL / 6 mice (n = 69) in order to establish the SCMM. After the appearance of the tumor in induced animals, they were divided into seven groups, of which three corresponded to the survival study: tumor control, Querc20 and Querc 50 and four other groups of the experiment itself: control without tumor, control with tumor, Querc20 and Querc50. During tumor progression, the diagnosis of CRC was established when weight loss ≥ 5% of the animal's body weight occurred. Querc (20 or 50 mg / kg of body weight) were administered to experimental mice via oral gavage. Serum levels of albumin and C-reactive protein (CRP) were measured by enzyme immunoassays. Muscle volume was measured using an ultrasound image and skeletal muscle strength was also investigated with the aid of a manual dynamometer. WAT and SMT samples were collected and subjected to gene expression analysis, using the quantitative real time polymerase chain reaction technique (RT- qPCR). Histomorphometric analysis was also performed with samples of WAT and SMT. The results showed that the mice treated with Querc50 exhibited a significant delay in the occurrence of CRC (p = 0.035); showed attenuation in body weight loss and better survival. The administration of Querc20 reduced the expression of C-reactive protein (CRP) in the serum of animals with SCMM compared to untreated animals (p <0.05). Treatment with Querc50 increased the expression of the TRIM55 gene and decreased from TRIM63 (p <0.05). In addition, a vertical ladder with an electrical stimulator for resistance exercise was developed in C57BL / 6 mice. It is concluded that the administration of Querc exhibited anti- cachectic effects an improved survival in C57BL / 6 mice submitted to SCMM. About registered patent is a result of product that assists in experimental research in rodents. These products are gains in scientific and technological innovation.