Presence of tumour inhibits the normal post-operative response in arginine and NO production in non-cachectic mice

Yvonne Lj Vissers , Maarten F von Meyenfeldt , Yvette C Luiking , Cornelis Hc Dejong , Wim A Buurman , Nicolaas Ep Deutz (1)

1 Maastricht University [Maastricht]

We recently described that cancer patients have low plasma arginine concentrations, even without weight loss being present, suggesting that decreased arginine availability may be a specific feature of the presence of tumour. Since arginine is important in post-operative repair, we hypothesized that abnormalities in arginine metabolism in cancer lead to an aberrant post-operative response in arginine and NO metabolism. To investigate this, we studied post-operative alterations in arginine and NO production and the acute phase response in MCA sarcoma-bearing mice. Controls, mice with small MCA tumours (<15% of carcass weight) and large MCA tumours (>15% of carcass weight) were studied, either with or without undergoing laparotomy. The stable isotopes L-[guanidino- 15}N 2}- 2}H 2}]arginine and L-[ureido- 15}N]citrulline were used to study whole-body arginine and NO production rates. Serum amyloid P component (SAP) concentrations were measured to assess the acute-phase response. Significance was tested using Mann-Whitney U test. In healthy FVB mice, laparotomy significantly increased whole-body arginine production (from 42±3 to 54±3 nmol/10g/min), NO production (from 1.1±0.1 to 1.4±0.2 nmol/10g/min) and levels of serum amyloid P component (from 4±1 to 115±23 ng/ml), while in all MCA tumour-bearing mice baseline values of arginine metabolism and [SAP] were already elevated and the response to laparotomy was absent. In conclusion, MCA tumour-bearing mice had a disturbed post-operative metabolic response as evidenced by attenuated post-operative arginine and NO production, concomitant with an attenuated acute-phase response. This indicates that altered arginine metabolism may be an important characteristic of the metabolic changes in cancer.

Mots clés: Medicine

Yvonne Lj Vissers, Maarten F von Meyenfeldt, Yvette C Luiking, Cornelis Hc Dejong, Wim A Buurman, et al.. Presence of tumour inhibits the normal post-operative response in arginine and NO production in non-cachectic mice. Clinical Science, 2007, 112 (10), pp.527-532. ⟨10.1042/CS20060340⟩. ⟨hal-00479355⟩