Effects of L-arginine-enriched total enteral nutrition on body weight gain, tumor growth, and in vivo concentrations of blood and tissue metabolites in rats inoculated with Walker tumor in the kidney

Abstract

Objective: We evaluated the effects of l-arginine-enriched total enteral nutrition (LATEN) on tumor-free and right kidney tumor-bearing rats through the determination of in vivo concentrations of metabolites to better understand intermediary metabolism in this model.

Methods: Rats were individually housed in wire cages within a controlled environment (25 degrees C and 50% relative humidity) and exposed to a 12-h light-and-dark cycle. Rats comprised the following groups: tumor-free on enteral nutrition plus l-amino acid (n = 8); tumor-free on enteral nutrition plus l-arginine (n = 8); tumor bearing on enteral nutrition plus l-amino acids (n = 8); and tumor bearing on enteral nutrition plus l-arginine (n = 8). Rats had their right kidneys inoculated with saline or tumor cells and were subjected to laparotomy or gastrostomy on day 1 and received chow diet for the next 2 days. Gastrostomy with enteral nutrition was performed on days 3 to 9. On day 9, body weight gain, tumor growth as volume, in vivo blood (microM/mL), and tissue (microM/g) metabolite concentrations were determined. The Mann-Whitney U test was used to test significance.

Results: LATEN in tumor-free rats decreased liver (0.25 +/- 0.03 versus 0.13 +/- 0.03 micromol/g, P < 0.05) and right kidney (0.13 +/- 0.1 versus 0.04 +/- 0.00 micromol/g, P < 0.05) ketone body concentrations. LATEN in tumor-bearing rats decreased blood pyruvate (0.17 +/- 0.01 versus 0.10 +/- 0.008 microM/mL, P < 0.005), lactate (5.2 +/- 0.3 versus 2.9 +/- 0.28 microM/mL, P < 0.01), and glucose (6.4 +/- 0.8 versus 3.7 +/- 0.5 microM/mL, P < 0.05). Glucose concentrations decreased in liver (13.9 +/- 2.0 versus 4.89 +/- 0.6 microM/g, P < 0.005) and tumor (3.5 +/- 0.8 versus 1.41 +/- 0.3 microM/g, P < 0.05). There were no changes in body weight gain (21 +/- 2.0 versus 30.3 +/- 3.6 g) or tumor growth (1.53 +/- 0.1 versus 1.26 +/- 0.01 cm(3)).

Conclusions: LATEN decreased ketone body concentrations in liver and kidney in tumor-free rats, possibly due to lower ketogenesis and decreased kidney uptake. In tumor-bearing rats, LATEN decreased lacticemia and glycemia and pyruvate blood concentrations. LATEN also reduced liver and tumor glucose concentrations in tumor-bearing animals. The possibility of LATEN-induced insulin and insulin-like growth factor-1 liberation signaling these changes is discussed.