Protective effect of natural flavonoids on rat peritoneal macrophages injury caused by asbestos fibers.
Exposure of macrophages to asbestos fibers resulted in enhancement of the production of oxygen radicals, determined by a lucigenin enhanced chemiluminescence (LEC) assay, a formation of thiobarbituric acid reactive substances (TBARS), a LDH release into the incubation mixture, and a rapid lysis of the cells. Rutin (Rut) and quercetin (Qr) were effective in inhibiting LEC, TBARS formation, and reducing peritoneal macrophages injury caused by asbestos. The concentrations pre-treatment of antioxidants that were required to prevent the injury of peritoneal macrophages caused by asbestos by 50% (IC50) were 90 microM and 290 microM for Qr and Rut, respectively. Both flavonoids were found to be oxidized during exposure of peritoneal macrophages to asbestos and the oxidation was SOD sensitive. The efficacy of flavonoids as antioxidant agents as well as superoxide ion scavengers was also evaluated using appropriate model systems, and both quercetin and rutin were found to be effective in scavenging O2.-. These findings indicate that flavonoids are able to prevent the respiratory burst in rat peritoneal macrophages exposed to asbestos at the stage of activated oxygen species generation, mainly as superoxide scavengers. On the basis of this study it was concluded that natural flavonoids quercetin and rutin would be promising drug candidates for a prophylactic asbestos-induced disease.
Kostyuk
V A
VA
Laboratory of Bioenergetics, Byelorussian State University, Minsk, Belarus.
Potapovich
A I
AI
Speransky
S D
SD
Maslova
G T
GT
D000166:Acridines; D000818:Animals; D001194:Asbestos / Q000037:antagonists & inhibitors / Q000633:toxicity*; D002251:Carbon Tetrachloride / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D007700:Kinetics; D007770:L-Lactate Dehydrogenase; D015227:Lipid Peroxidation / Q000187:drug effects; D008163:Luminescent Measurements; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism*; D019016:Mineral Fibers; D010084:Oxidation-Reduction; D011794:Quercetin / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D016897:Respiratory Burst / Q000187:drug effects*; D012431:Rutin / Q000494:pharmacology*; D017392:Thiobarbituric Acid Reactive Substances
D000166:Acridines; D019016:Mineral Fibers; D017392:Thiobarbituric Acid Reactive Substances; D001194:Asbestos; C033472:10,10'-dimethyl-9,9'-biacridinium; D012431:Rutin; D011794:Quercetin; D002251:Carbon Tetrachloride; D007770:L-Lactate Dehydrogenase