Mariëlle P K J Engelen1, V Suzanne Klimberg2, Arianna Allasia3, Nicolaas E P Deutz4. 1. Center for Translational Research on Aging and Longevity, Dept. of Health and Kinesiology, Texas A&M University, College Station, TX, USA; Dept. of Geriatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA. Electronic address: mpkj.engelen@ctral.org. 2. Division of Breast Surgical Oncology, Dept. of Surgery, University of Arkansas for Medical Sciences, Little Rock, AR, USA. 3. Dept. of Geriatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA. 4. Center for Translational Research on Aging and Longevity, Dept. of Health and Kinesiology, Texas A&M University, College Station, TX, USA; Dept. of Geriatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
Abstract
BACKGROUND & AIMS: Plasma arginine (ARG) levels are reduced in breast cancer, suggesting diminished systemic ARG availability. ARG and its product nitric oxide (NO) are important in early postoperative recovery due to its roles in immune function and wound healing. It remains unclear whether major surgery further diminishes systemic ARG availability due to enhanced ARG catabolism and/or insufficient endogenous ARG synthesis negatively affecting NO synthesis in patients with early stage breast cancer. METHODS: In 9 women with early stage breast malignancy and 9 healthy women with genetic predisposition to breast cancer, whole body ARG and citrulline (CIT) rates of appearances were measured to determine their production rates prior to and within 24 h after major breast surgery by stable isotope methodology in the postabsorptive and postprandial state. The conversions of CIT > ARG, ARG > CIT, and ARG > Urea (markers of de novo ARG and NO synthesis, arginase activity, respectively), and ARG clearance (reflecting ARG disposal capacity) were calculated. RESULTS: Prior to surgery, plasma ARG, CIT and glutamine concentrations were lower in cancer (P < 0.05) but no differences were found in the rate of appearances of ARG, CIT and their conversions. Surgery increased ARG clearance and reduced CIT rate of appearance, conversion of CIT > ARG (P < 0.001), and plasma ARG, CIT, ornithine concentrations (P < 0.001). Furthermore, postprandial increase in ARG > CIT conversion (P < 0.05), plasma ARG (P < 0.001) and CIT (P = 0.06) concentrations were lower after surgery. The cancer group had lower values for postprandial increase in ARG > CIT conversion, plasma CIT (P < 0.05) and glutamine concentrations (P = 0.08). CONCLUSIONS: Major surgery in early stage breast cancer further reduces systemic ARG availability in the early phase of recovery due to a combined process of increased ARG catabolism and impaired endogenous ARG synthesis. The suppressed postprandial NO increase in early stage cancer suggests that specific nutritional approaches are advised to increase ARG availability after major surgery although the effects on postoperative recovery remain unclear. This trial was registered at clinicaltrials.gov as NCT00497380.
BACKGROUND & AIMS: Plasma arginine (ARG) levels are reduced in breast cancer, suggesting diminished systemic ARG availability. ARG and its product nitric oxide (NO) are important in early postoperative recovery due to its roles in immune function and wound healing. It remains unclear whether major surgery further diminishes systemic ARG availability due to enhanced ARG catabolism and/or insufficient endogenous ARG synthesis negatively affecting NO synthesis in patients with early stage breast cancer. METHODS: In 9 women with early stage breast malignancy and 9 healthy women with genetic predisposition to breast cancer, whole body ARG and citrulline (CIT) rates of appearances were measured to determine their production rates prior to and within 24 h after major breast surgery by stable isotope methodology in the postabsorptive and postprandial state. The conversions of CIT > ARG, ARG > CIT, and ARG > Urea (markers of de novo ARG and NO synthesis, arginase activity, respectively), and ARG clearance (reflecting ARG disposal capacity) were calculated. RESULTS: Prior to surgery, plasma ARG, CIT and glutamine concentrations were lower in cancer (P < 0.05) but no differences were found in the rate of appearances of ARG, CIT and their conversions. Surgery increased ARG clearance and reduced CIT rate of appearance, conversion of CIT > ARG (P < 0.001), and plasma ARG, CIT, ornithine concentrations (P < 0.001). Furthermore, postprandial increase in ARG > CIT conversion (P < 0.05), plasma ARG (P < 0.001) and CIT (P = 0.06) concentrations were lower after surgery. The cancer group had lower values for postprandial increase in ARG > CIT conversion, plasma CIT (P < 0.05) and glutamine concentrations (P = 0.08). CONCLUSIONS: Major surgery in early stage breast cancer further reduces systemic ARG availability in the early phase of recovery due to a combined process of increased ARG catabolism and impaired endogenous ARG synthesis. The suppressed postprandial NO increase in early stage cancer suggests that specific nutritional approaches are advised to increase ARG availability after major surgery although the effects on postoperative recovery remain unclear. This trial was registered at clinicaltrials.gov as NCT00497380.
Authors: Iris B J G Debats; Darren Booi; Nicolaas E P Deutz; Wim A Buurman; Willy D Boeckx; Rene R W J van der Hulst Journal: J Surg Res Date: 2006-04-21 Impact factor: 2.192
Authors: A C Bernard; S K Mistry; S M Morris; W E O'Brien; B J Tsuei; M E Maley; L A Shirley; P A Kearney; B R Boulanger; J B Ochoa Journal: Shock Date: 2001-03 Impact factor: 3.454
Authors: Yvonne L J Vissers; Maarten F von Meyenfeldt; Yvette C Luiking; Cornelis H C Dejong; Wim A Buurman; Nicolaas E P Deutz Journal: Clin Sci (Lond) Date: 2007-05 Impact factor: 6.124
Authors: C Marcela Diaz-Montero; Mohamed Labib Salem; Michael I Nishimura; Elizabeth Garrett-Mayer; David J Cole; Alberto J Montero Journal: Cancer Immunol Immunother Date: 2008-04-30 Impact factor: 6.968
Authors: Mariëlle P K J Engelen; Renate Jonker; John J Thaden; Gabriella A M Ten Have; Moon Sun Jeon; Srinivasan Dasarathy; Nicolaas E P Deutz Journal: Clin Nutr Date: 2020-01-29 Impact factor: 7.324
Authors: Abbas Salihi; Mohammed A Al-Naqshabandi; Zhikal Omar Khudhur; Zjwan Housein; Harmand A Hama; Ramyar M Abdullah; Bashdar Mahmud Hussen; Twana Alkasalias Journal: Mol Med Rep Date: 2022-05-26 Impact factor: 3.423
Authors: Tomasz M Grzywa; Anna Sosnowska; Paweł Matryba; Zuzanna Rydzynska; Marcin Jasinski; Dominika Nowis; Jakub Golab Journal: Front Immunol Date: 2020-05-15 Impact factor: 7.561