Glucomannan reduces neutrophil free radical production in vitro and in rats with adjuvant arthritis.
The effect of glucomannan (GM), a natural polysaccharide isolated from the yeast Candida utilis, on reactive oxygen species (ROS) generation in human neutrophils in vitro and in rats with Mycobacterium butyricum induced adjuvant arthritis (AA) was tested by the luminol/isoluminol-enhanced chemiluminescence (CL) method. In vitro, GM (500 microg/ml) significantly decreased spontaneous CL of human whole blood, while PMA (4beta-phorbol-12beta-myristate-alpha13acetate)-stimulated CL was decreased by GM in the concentrations of 100 and 500 microg/ml. To specify the site of action of GM, its effect on extra- and intracellular ROS generation in isolated neutrophils was evaluated. GM significantly decreased spontaneous and PMA-stimulated CL and it was more effective extracellularly than intracellularly. In vivo experiments included healthy animals as controls, arthritic animals without any drug administration, and arthritic animals with GM administration (once daily in the oral dose of 15 mg/kg, over a period of 28 days). On day 28, CL in whole blood, spleen and joint was monitored. Arthritic animals treated with GM showed decrease in spontaneous and PMA-stimulated CL of whole blood as well as CL of the joint, in comparison with untreated animals. The obtained findings demonstrated an antioxidant effect of GM in vitro and in rats with AA, which may be due to its free radical scavenger activity and to interaction with different receptors and/or modulation of postreceptor intracellular signalling pathways. The specific physicochemical parameters, such as structure of GM, its low molecular weight and good water solubility, play an important role in the above effects.
Drábiková
Katarína
K
Institute of Experimental Pharmacology, Slovak Academy of Sciences, Dúbravská cesta 9, 84104 Bratislava, Slovak Republic. Katarina.Drabikova@savba.sk
Perecko
Tomás
T
Nosál
Radomír
R
Bauerová
Katarína
K
Ponist
Silvester
S
Mihalová
Danica
D
Kogan
Grigorij
G
Jancinová
Viera
V
D000328:Adult; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology*; D001169:Arthritis, Experimental / Q000378:metabolism* / Q000382:microbiology; D004305:Dose-Response Relationship, Drug; D005609:Free Radicals / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D008163:Luminescent Measurements; D008297:Male; D008351:Mannans / Q000008:administration & dosage / Q000494:pharmacology*; D008875:Middle Aged; D009161:Mycobacterium; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D011917:Rats, Inbred Lew; D017382:Reactive Oxygen Species / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000031:analogs & derivatives / Q000494:pharmacology; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D000975:Antioxidants; D005609:Free Radicals; D008351:Mannans; D017382:Reactive Oxygen Species; D017392:Thiobarbituric Acid Reactive Substances; C022901:(1-6)-alpha-glucomannan; C016658:phorbolol myristate acetate; D013755:Tetradecanoylphorbol Acetate