Efeitos do resveratrol na caquexia associada ao câncer: ensaios in vivo no modelo tumoral murino singênico de melanoma cutâneo em camundongos C57BL/6

Abstract

Cachexia is a paraneoplastic syndrome associated with cancer progression, characterized by anorexia and involuntary weight loss, especially skeletal and adipose mass, with a consequent negative impact on the antineoplastic therapeutic response, the quality of life and the survival time of individuals with cancer . The present study evaluated the methodological aspects related to the experimental cachexia associated with the syngeneic murine tumoral model of cutaneous melanoma in C57Bl / 6 mice. Additionally, investigate the potential antico-ectic effects promoted by resveratrol in this cancer-associated cachexia model. Through a systematic review of the literature, we contemplated methodological analyzes of cachexia induction in murine model, pharmacological approaches and the main findings related to the diagnosis of the disease. For this, titles and keywords were consulted in electronic databases (MEDLINE, PUBMED, EMBASE, Scopus, SciELO and Web of Science). Each selected study was evaluated individually and the methodological quality of the studies using the Jadad scale. Initially, 57 publications were selected, of which seven met the inclusion criteria. The most common model of MC in mice has been established with subcutaneous inoculation of B16F10 murine melanoma cells in the dorsal region of female C57BL6 animals. CMrelated cachexia occurs with tumor progression and the diagnosis of cachexia is based primarily on body weight associated with most studies with gastrocnemius muscle mass or visceral adipose tissue. The anticancer therapeutic approach related to cutaneous melanoma (MC) has been performed only with anti-inflammatory drugs. Treatments that promote anticoagulant effects are those that also reduce tumor volume concomitantly. In conclusion, few parameters are used to define cachexia in the mouse model, and the effect of antiinflammatory drugs on the mouse CM model associated with cachexia is conditioned to tumor reduction. The objective of this study was to investigate the anticoagulant effects promoted by the use of resveratrol (Resv.) In target tissues of the syndrome and in the survival of C57B1 / 6 mice submitted to the syngeneic tumor model of cachexia associated with experimental cutaneous melanoma. Murine B16F10 cells were inoculated into the flank of fifty-eight female C57BL / 6 mice. The diagnosis of CRC was established individually considering weight loss ≥ 5%. The resv. was administered at 200 and 400 mg / kg body weight using oral gavage in control and experimental mice for 12 days. Water and food intake, body weight and tumor size were measured daily. Serum levels of albumin and C-reactive protein (CRP) were assessed by enzyme immunoassays. Skeletal muscle strength, volume and mass were evaluated using a grip force gauge, a high frequency ultrasound device and an analytical balance, respectively. Samples of skeletal muscle, white and brown adipose tissue were collected and submitted to morphometric analysis and gene expression. Mice treated with resv. (p <0.01, p <0.001 and p <0.18, respectively) were associated with a delay in the establishment of CRC, with body weight gain, skeletal muscle (ME) and improvement in survival. Increased ME volume, muscle strength and preserved the loss of muscle fibers (200mg / kg, p <0.001 and 400mg / kg, p <0.01). Reduced TAB weight and adipocyte area (p <0.01). It promoted a decrease in chronic inflammation of low grade (200mg / kg, p <0.001, and 400mg / kg, p <0.01). It was found that the administration of resv. in C57BL / 6 mice in a cachexia model related to the syngeneic MC, has anticoagulant effects and improves survival.