title: Combination of anti-tuberculosis drugs with vitamin C or NAC against different Staphylococcus aureus and Mycobacterium tuberculosis strains.
abstract: BACKGROUND
  Hepatotoxicity due to anti tuberculosis drugs, rifampin and isoniazid, is a major problem in tuberculosis patients. Vitamin C, an antioxidant, and N-acetyl cysteine (NAC), a scavenger of active metabolites, reduce the hepatotoxicity. The aim of present study was to investigate the effect of vitamin C and NAC individually on the antibacterial activity of anti tuberculosis drugs against Mycobacterium tuberculosis and Staphylococcus aureus strains.
  
  
  METHODS
  The MICs of each compound against all strains were determined in 96 wells plate. Rifampin was tested at serial two fold concentrations alone or in combination with NAC or vitamin C.
  
  
  RESULTS
  The MIC of rifampin against different strains of S. aureus was 0.008-0.032 μg/ml. The MIC of rifampin and isoniazid against M. tuberculosis strains were 40 and 0.2 μg/ml, respectively. Vitamin C and NAC had no antibacterial activity against all strains. MIC of rifampin was reduced two fold by combination with vitamin C for all S. aureus strains, while NAC did not affect the antibacterial activity of rifampin. Vitamin C and NAC had remarkable effects on the antibacterial activity of anti-tuberculosis drugs against M. tuberculosis.
  
  
  CONCLUSIONS
  Synergistic effects were observed between rifampin or isoniazid and vitamin C against all tested strains. However, combination therapy of rifampin and isoniazid with NAC was not being effective. This study highlighted the advantages of combination of anti-tuberculosis drugs and vitamin C to eradicate the microbial infections.
authors.affiliation: Department of Pharmaceutical Control, Students Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Bahman
authors.initials: B
authors.lastname: Khameneh
authors.affiliation: Biotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Bibi Sedigheh
authors.initials: BS
authors.lastname: Fazly Bazzaz
authors.affiliation: Students Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Alireza
authors.initials: A
authors.lastname: Amani
authors.affiliation: Students Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Javad
authors.initials: J
authors.lastname: Rostami
authors.affiliation: Medical Toxicology Research Center, Mashhad University of Medical Sciences, Mashhad, IR Iran; Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address: vahdatin@mums.ac.ir.
authors.forename: Nasser
authors.initials: N
authors.lastname: Vahdati-Mashhadian
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology*; D000995:Antitubercular Agents / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology*; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D006801:Humans; D007538:Isoniazid / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000502:physiology; D012293:Rifampin / Q000494:pharmacology; D013203:Staphylococcal Infections / Q000188:drug therapy / Q000382:microbiology*; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000502:physiology; D014376:Tuberculosis / Q000188:drug therapy / Q000382:microbiology*
chemical_list: D000995:Antitubercular Agents; D001205:Ascorbic Acid; D007538:Isoniazid; D012293:Rifampin; D000111:Acetylcysteine
keywords: Isoniazid; Mycobacterium tuberculosis; N-acetyl cysteine; Rifampin; Staphylococcus aureus; Vitamin C