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Effect of citrulline on cultured macrophages from Zucker Diabetic Fatty (ZDF) rats
Author(s) -
Bonhomme Sandra,
Kohler Josephine,
Dumez Celine,
Breuillard Charlotte,
Leplenier Servane,
Couderc Remy,
Cynober Luc,
Darquy Sylviane
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.466.6
Subject(s) - medicine , endocrinology , nitric oxide , immune system , arginine , type 2 diabetes , diabetes mellitus , citrulline , western blot , chemistry , immunology , biochemistry , amino acid , gene
Obese and type 2 diabetic patients present metabolic and immune impairments that weaken response to aggression and infectious complications. Arginine (Arg), which level is depressed in diabetes, has immune properties and is essential in situations of stress. In particular, it is the precursor of nitric oxide (NO). Since administration of Arg is associated with adverse effects, the use of citrulline (Cit) as an indirect progenitor for NO is of particular interest. Objectives: To evaluate the effect of Cit on macrophages from ZDF control fa/+ and diabetic‐obese fa/fa rats. Peritoneal macrophages (510 5 cells) from fa/+ and fa/fa rats were cultured with 0.5, 1 and 2 mmol/l Cit concentrations for 24 h (n=12/group). NO and TNFα were measured in the supernatant. In cell extracts, iNOS protein expression was evaluated by Western blot. Results: In the fa/+ rats NO production was related to Cit concentration, and TNFα concentration remained constant. In fa/fa rats NO production increased with 1 mmol/l of Cit, and TNFα production decreased with high Cit concentration. Conclusions: Cit can act as a precursor for Arg in macrophage NO production. Like arginine, Cit has an anti‐inflammatory effect by decreasing TNFα production and is able to restore NO production in inflammatory situations such as diabetes and obesity. Cit administration can be considered as an alternative to arginine supplementation in clinical use.