title: Arginine Supplementation Induces Arginase Activity and Inhibits TNF-α Synthesis in Mice Spleen Macrophages After Intestinal Obstruction.
abstract: BACKGROUND
  The purpose of this study was to assess the effect of arginine supplementation on arginase activity, tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10) synthesis in cultured splenic macrophages from a murine model of intestinal obstruction (IO). The effects of nitric oxide synthase (iNOS) inhibition were also studied using iNOS knockout animals.
  
  
  METHODS
  Male C57BL6/J wild-type (WT) and iNOS knockout (iNOS-/-) mice were randomized into 6 groups: Sham and Sham-/- (standard chow), IO and IO-/- (standard chow + IO), and Arg and Arg-/- (standard chow supplemented with arginine + IO). After 7 days of treatment with standard or supplemented chow, IO was induced. Arginase activity as well as TNF-α and IL-10 levels were analyzed in splenic macrophage cultures.
  
  
  RESULTS
  Arginine supplementation and the absence of iNOS increased arginase activity in splenic macrophages (Arg, IO-/-, and Arg-/- groups vs the Sham group; P < .05). Arginine was also related to a decrease in TNF-α levels (Arg vs IO group, P < .05) and maintenance of IL-10 levels (Arg vs other groups, P > .05). The inhibition of iNOS did not result in effects on the concentration of cytokines (Sham-/-, IO-/-, and Arg-/- vs other, P < .05).
  
  
  CONCLUSIONS
  Arginine supplementation and iNOS inhibition led to increased arginase activity. Arginine availability decreased plasma TNF-α levels, which may be directly related to nitric oxide derived from arginine.
authors.affiliation: Department of Clinical Analysis and Toxicology, Pharmacy School, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: Iara Eliza Pacífico
authors.initials: IE
authors.lastname: Quirino
authors.affiliation: Department of Biochemistry and Immunology, Biologic Sciences Institute, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: Matheus Batista Heitor
authors.initials: MB
authors.lastname: Carneiro
authors.affiliation: Department of Clinical Analysis and Toxicology, Pharmacy School, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: Valbert Nascimento
authors.initials: VN
authors.lastname: Cardoso
authors.affiliation: Department of Clinical Analysis and Toxicology, Pharmacy School, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: Rosana
authors.initials: R
authors.lastname: das Graças Carvalho Dos Santos
authors.affiliation: Department of Biochemistry and Immunology, Biologic Sciences Institute, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: Leda Quercia
authors.initials: LQ
authors.lastname: Vieira
authors.affiliation: Renè Rachou Research Center, Fundação Oswaldo Cruz, Belo Horizonte, MG, Brazil Department of Parasitology, Biologic Sciences Institute Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: Jacqueline Araújo
authors.initials: JA
authors.lastname: Fiuza
authors.affiliation: Department of Biochemistry and Immunology, Biologic Sciences Institute, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: Jacqueline Isaura
authors.initials: JI
authors.lastname: Alvarez-Leite
authors.affiliation: Department of Nutrition, Nursing School, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil simonenutufmg@gmail.com.
authors.forename: Simone
authors.initials: S
authors.lastname: de Vasconcelos Generoso
authors.affiliation: Department of Surgery, Medical School, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: Maria Isabel
authors.initials: MI
authors.lastname: Correia
mesh_terms: D000818:Animals; D001119:Arginase / Q000378:metabolism*; D001120:Arginine / Q000494:pharmacology*; D019587:Dietary Supplements; D016753:Interleukin-10 / Q000378:metabolism; D007415:Intestinal Obstruction / Q000188:drug therapy*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000378:metabolism; D013154:Spleen / Q000166:cytology / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D009569:Nitric Oxide; D001120:Arginine; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D001119:Arginase
keywords: arginase; immune modulation; inducible nitric oxide synthase