PMID- 16304167
OWN - NLM
STAT- MEDLINE
DCOM- 20060314
LR  - 20240412
IS  - 0066-4804 (Print)
IS  - 1098-6596 (Electronic)
IS  - 0066-4804 (Linking)
VI  - 49
IP  - 12
DP  - 2005 Dec
TI  - Interaction of rifalazil with oxidant-generating systems of human 
      polymorphonuclear neutrophils.
PG  - 5018-23
AB  - It is well acknowledged that ansamycins display immunosuppressive and 
      anti-inflammatory properties in vitro and in vivo. Rifalazil, a new ansamycin 
      derivative, has not been studied in the context of inflammation. In particular, 
      there are no data on the possible interference of rifalazil with oxidant 
      production by phagocytes. We have compared the antioxidant properties of 
      rifalazil to those of rifampin, a drug well known in this context, by using 
      cellular and acellular oxidant-generating systems. Oxidant production by 
      polymorphonuclear neutrophils was measured in terms of cytochrome c reduction, 
      lucigenin-amplified chemiluminescence (Lu-ACL), and the 2',7'-dichlorofluorescin 
      diacetate H2 (DCFDA-H2) technique (intracellular oxidant production). Rifalazil 
      impaired O2- production in a concentration-dependent manner, with 50% inhibitory 
      concentrations (IC50) (concentrations which inhibit 50% of the response) of 5.4 
      (30 and 60 min of incubation) and 6.4 (30 min) mg/liter, respectively, for 
      phorbol myristate acetate (PMA) and formyl-methionyl-leucyl-phenylalanine (fMLP) 
      stimulation. In agreement with the published fMLP-like activity of rifampin, the 
      inhibitory effect of rifampin was significantly greater for fMLP (IC50 of 5.6 
      mg/liter) than for PMA (IC50 of 58 mg/liter) stimulation. Alteration of 
      intracellular oxidant production was also observed with IC50 values similar to 
      those obtained by the cytochrome assay. In addition, rifalazil and rifampin (> or 
      = 25 mg/liter) scavenged O2-, as demonstrated by the acellular 
      (hypoxanthine-xanthine oxidase) system. Interference with light detection systems 
      was evidenced for both drugs by Lu-ACL. The clinical relevance of the antioxidant 
      effect of rifalazil demonstrated in vitro, in particular its potential 
      anti-inflammatory activity, requires further investigation.
FAU - Labro, M T
AU  - Labro MT
AD  - INSERM U479, CHU Xavier Bichat, 16 rue Henri Huchard, 75018 Paris, France. 
      mtlabro@wanadoo.fr
FAU - Ollivier, V
AU  - Ollivier V
FAU - Babin-Chevaye, C
AU  - Babin-Chevaye C
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Antimicrob Agents Chemother
JT  - Antimicrobial agents and chemotherapy
JID - 0315061
RN  - 0 (Anti-Bacterial Agents)
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Oxidants)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Rifamycins)
RN  - 11062-77-4 (Superoxides)
RN  - 129791-92-0 (KRM 1648)
SB  - IM
MH  - Anti-Bacterial Agents/administration & dosage/pharmacology
MH  - Anti-Inflammatory Agents/*pharmacology
MH  - Cell Survival/drug effects
MH  - Humans
MH  - Neutrophils/cytology/*drug effects/metabolism
MH  - Oxidants/*metabolism
MH  - Reactive Oxygen Species/metabolism
MH  - Rifamycins/administration & dosage/*pharmacology
MH  - Superoxides/metabolism
PMC - PMC1315961
EDAT- 2005/11/24 09:00
MHDA- 2006/03/15 09:00
PMCR- 2005/12/01
CRDT- 2005/11/24 09:00
PHST- 2005/11/24 09:00 [pubmed]
PHST- 2006/03/15 09:00 [medline]
PHST- 2005/11/24 09:00 [entrez]
PHST- 2005/12/01 00:00 [pmc-release]
AID - 49/12/5018 [pii]
AID - 0867-05 [pii]
AID - 10.1128/AAC.49.12.5018-5023.2005 [doi]
PST - ppublish
SO  - Antimicrob Agents Chemother. 2005 Dec;49(12):5018-23. doi: 
      10.1128/AAC.49.12.5018-5023.2005.