Alterações metabólicas em ratos com implante gástrico de carcinossarcoma de Walker 256 submetidos a hipertermia

Abstract

Nowadays, in Ceará, gastdc cancer is a public health problem with high rate of mortality. Considering new therapeutic approaches for gastíc cancer, clinical hyperfhermia have been well established and proposed in other countnes. Hyperthemúa (HT) may dü-ecüy affect ceUular functions or damage regulatory and metabolic systems, producing secondary effects. Thermal sensitivity of tumors depends on tumor pH, energy and nutntional status. We investigated if the tumor per si and the HT affect the tumor host metabolic processes. Murines with ti-ansplantable tumors have been used aiming to investigate how these physiological parameters enhance fhennal sensitivity. In this work, we studied the metabolism in blood, stomach and Uver samples of rats bearmg Walker 256 tumor (W256) with continuous peritoneal hyperthermic perfúsion. Cells from W256 were injected in a tube along the esophagus to the stomach in rats. Mucosal lesions were mduced by clanipmg the stomach foUowed by tumor implantation and growth. Rats were operated under ether anesthesia. Sham-operated ammals were used as conto'ols. Normothermia (NT-^ 37°-38°C) and the HT (41°-^2°C) were perfonned under ketanúne and xüazane anesthesia, during 60 minutes. Arterial blood, either stomach and liver samples was collected immediately (TO), thirty (T30), and sixty minutes (T60) after NT or HT. Metabolites were extracted m HCL04 0,75 M. Lactate, pyruvate, glucose and ketone bodies (KB) were measured using standard enzymatic methods. Statistical significance was examined using ANO VA (p<0,05) and Fisher's test. We found an increase on levels of total KB at blood (0,48±0,03 ^iM), hepatic (0,89±0,02 {AM) and gastric (0,54±0,01 pM) samples in rats bearing W256 under HT; and a decreased (p<0,03) of pymvate concentrations. We reported high glucaemia in tumor groups (12,90±0,45 (^M) and the liver concentrations of glucose (22,12±0,17 pM) was much higher m sham operated (HT) group than tumor group after HT. The lactate level at stomach (5,74dh0,27 ^iM) increased m all ^-oups under HT, predommantly at T30. We concluded that HT induced aã ünpainnent on glycolytic pathway m rats bearing W256, and increased (3-hydroxybutirate and acetoacetate levels; thus we suggest that lactic acid added to KB play the major role for the increased acidity in heated tumor and contiibutes to tumor ceU apoptosis.