Changes in blood metabolic parameters during the development of Walker‐256 tumour‐induced cachexia in rats are not caused by decreased food intake

Abstract

Blood metabolic parameters of Walker-256 tumour-bearing rats, on days 5, 8, 11 and 14 after implantation of tumour, were compared with those of rats without tumour fed ad libitum (free-fed control) or with reduced feeding (pair-fed control), similar to the anorexic tumour-bearing rats. Cachexia parameters and tumour mass also were investigated. In general, especially on day 14 after implantation of tumour, there was reduction of body mass, gastrocnemius muscle mass, food intake and glycemia and increase of blood triacylglycerol, free fatty acids, lactate and urea, compared with free-fed controls rats. These changes did not occur in pair-fed control, except a slight reduction of glycemia. Pair-fed control showed no significant changes in blood cholesterol and glycerol in comparison with free-fed control, although there was reduction of cholesterol and increase of blood glycerol on day 14 after tumour implantation compared with pair-fed control. The results demonstrate that, besides the characteristic signs of the cachexia syndrome such as anorexia, weight loss and muscle catabolism, Walker-256 tumour-bearing rats show several blood metabolic alterations, some of which begin as early as day 5 after implantation of tumour, and are accentuated during the development of cachexia. Evidence that the alterations of blood metabolic parameters of tumour-bearing rats were not found in pair-fed control indicate that they were not caused by decreased food intake. These changes were probably mediated by factors produced by tumour or host tissue in response to the presence of tumour.

Early treatment with metformin induces resistance against tumor growth in adult rats

“…Thus, a batch of rats treated with water or metformin since weaning, at 101 d old, and another batch of animals treated with water or metformin since adulthood, at 140 d old, were inoculated subcutaneously (8.0 £ 10 7 viable tumor cells/animal) into their right rear flanks. 52 Animals from 2 different ages groups, with or without metformin treatment, were inoculated at the same time with the same batch of tumor cells.…”

Protective Effect of Metformin Against Walker 256 Tumor Growth is Not Dependent on Metabolism Improvement

“…After one week the cells were collected, centrifuged, resuspended in phosphate buffered saline (PBS; 16.5 mmol l -1 of phosphate, 137 mmol l -1 of NaCl and 2.7 mmol l -1 of KCl), pH 7.4, and the cell viability was evaluated using the method of trypan blue exclusion. A batch of Control and MSG rats, at 101 days old, treated or untreated with metformin were inoculated subcutaneously with 8.0 x 10 7 viable tumor cells/animal into their right rear flanks [25]. The inoculation of the Walker 256 tumor cells was performed 24-h after metformin treatment stopped, as shown in Fig.…”

“…The loss of bw was calculated as follows: LBW (%) = 100 × (bwi - bwf + tm + gbw)/(bwi + gbw); where LBW: loss of body weight; bwi: initial body weight (g), and bwf: final body weight (g) of rats with tumor; tm: tumor mass (g); and gbw: body weight gain (g) of rat without tumor during the 14 days the experiment. The rats were considered cachectic when the LBW was higher than 10% [25]. …”

Chronic Glibenclamide Treatment Attenuates Walker-256 Tumour Growth in Prediabetic Obese Rats

“…At the end of the treatment period, the 101-day-old animals from each experimental group were inoculated subcutaneously with 8.0 x 10 7 viable tumour cells/animal in the right rear flank [19, 20]. The inoculation of the Walker-256 tumour cells was performed 24 h after the end of treatment with Gli.…”