title: N-acetyl-L-cysteine combined with mesalamine in the treatment of ulcerative colitis: randomized, placebo-controlled pilot study.
abstract: OBJECTIVE
  To evaluate the effectiveness and safety of oral N-acetyl-L-cysteine (NAC) co-administration with mesalamine in ulcerative colitis (UC) patients.
  
  
  METHODS
  Thirty seven patients with mild to moderate UC were randomized to receive a four-wk course of oral mesalamine (2.4 g/d) plus N-acetyl-L-cysteine (0.8 g/d) (group A) or mesalamine plus placebo (group B). Patients were monitored using the Modified Truelove-Witts Severity Index (MTWSI). The primary endpoint was clinical remission (MTWSI < or = 2) at 4 wk. Secondary endpoints were clinical response (defined as a reduction from baseline in the MTWSI of > or = 2 points) and drug safety. The serum TNF-alpha, interleukin-6, interleukin-8 and MCP-1 were evaluated at baseline and at 4 wk of treatment.
  
  
  RESULTS
  Analysis per-protocol criteria showed clinical remission rates of 63% and 50% after 4 wk treatment with mesalamine plus N-acetyl-L-cysteine (group A) and mesalamine plus placebo (group B) respectively (OR = 1.71; 95% CI: 0.46 to 6.36; P = 0.19; NNT = 7.7). Analysis of variance (ANOVA) of data indicated a significant reduction of MTWSI in group A (P = 0.046) with respect to basal condition without significant changes in the group B (P = 0.735) during treatment. Clinical responses were 66% (group A) vs 44% (group B) after 4 wk of treatment (OR = 2.5; 95% CI: 0.64 to 9.65; P = 0.11; NNT = 4.5). Clinical improvement in group A correlated with a decrease of IL-8 and MCP-1. Rates of adverse events did not differ significantly between both groups.
  
  
  CONCLUSIONS
  In group A (oral NAC combined with mesalamine) contrarily to group B (mesalamine alone), the clinical improvement correlates with a decrease of chemokines such as MCP-1 and IL-8. NAC addition not produced any side effects.
authors.affiliation: Unidad de Toxicologia Molecular Hepatica, Department de Bioquimica & Biologia Molecular, Universidad de Alcala, E-28871, Alcala de Henares, Spain. luis.gonzalez@uah.es
authors.forename: Luis G
authors.initials: LG
authors.lastname: Guijarro
authors.forename: Jose
authors.initials: J
authors.lastname: Mate
authors.forename: Javier P
authors.initials: JP
authors.lastname: Gisbert
authors.forename: Jose Luis
authors.initials: JL
authors.lastname: Perez-Calle
authors.forename: Ignacio
authors.initials: I
authors.lastname: Marin-Jimenez
authors.forename: Encarna
authors.initials: E
authors.lastname: Arriaza
authors.forename: Tomas
authors.initials: T
authors.lastname: Olleros
authors.forename: Mario
authors.initials: M
authors.lastname: Delgado
authors.forename: Maria S
authors.initials: MS
authors.lastname: Castillejo
authors.forename: David
authors.initials: D
authors.lastname: Prieto-Merino
authors.forename: Venancio
authors.initials: V
authors.lastname: Gonzalez Lara
authors.forename: Amado-Salvador
authors.initials: AS
authors.lastname: Pena
mesh_terms: D000111:Acetylcysteine / Q000009:adverse effects / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000627:therapeutic use*; D018932:Chemokine CCL2 / Q000097:blood; D003093:Colitis, Ulcerative / Q000097:blood / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D005260:Female; D016166:Free Radical Scavengers / Q000009:adverse effects / Q000627:therapeutic use*; D005978:Glutathione / Q000097:blood; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood; D008297:Male; D019804:Mesalamine / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D010865:Pilot Projects; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D016166:Free Radical Scavengers; D015850:Interleukin-6; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D019804:Mesalamine; D005978:Glutathione; D000111:Acetylcysteine