Citrulline and arginine increase the growth of the ward colon tumor in parenterally fed rats

Abstract

Arginine is considered a necessary component of parenteral regimens because of the high nitrogen intake. The effect of arginine on tumor growth, however, is controversial. Our results suggest that substituting ornithine for arginine in parenteral regimens will ameliorate an arginine‐related increase in growth of a Ward colon tumor. Although a metabolite of arginine and ornithine in the urea cycle, citrulline has differential effects on growth in vivo and in vitro. To evaluate the effect of citrulline on tumor growth, Ward colon tumor‐bearing rats were given parenteral nutrition regimens with ornithine (ENO) or citrulline (ENC) substituted for arginine (ENA). The plasma amino acid profiles and tumor growth were compared. Tumor growth was evaluated by changes in the calculated tumor weight over an eight‐day feeding period. The initial tumor weight for all groups was equivalent. The final tumor weights of rats receiving ENA (14.1 ± 3.3 g) and ENC (12.7 ± 1.4 g) were significantly (p < 0.05) greater than those of rats receiving ENO (8.8 ±2.0 g) or the chow‐fed controls (8.9 ±2.1 g). Plasma concentrations of arginine, ornithine, and citrulline were significantly increased when the respective amino acids were components of the regimen. The plasma arginine concentration of rats receiving ENO (60.4 ± 3.8 μM) was significantly lower than the control (149.9 ± 24.1 μM). The plasma arginine concentration was significantly increased for rats receiving ENA (280.3 ± 68.1 μM) and was even further increased for rats receiving ENC (481.8 ± 94.1 μM). The plasma glutamine concentration for ENO rats (536.4 ± 37.5 μM) was significantly higher than that for controls (483.5 ± 53.5 μM). The plasma glutamine concentration for rats receiving ENA (402.3 ± 50.3 μM) and ENC (379.9 ± 37.6 μM) was significantly lower than that of the control fed chow. These results further implicate arginine as a major factor for the total parenteral nutrition‐enhanced growth of the Ward colon tumor.