Antiinflammatory reactivity of copper(I)-thionein.
In unseparated human blood the reactivity of yeast copper (I)-thionein on TPA-activated polymorphonuclear leukocytes was evaluated and compared with low Mr copper chelates exerting Cu2Zn2 superoxide dismutase mimetic activity. Cu, 18 microM, in the form of Cu-thionein was sufficient to inhibit the superoxide production of activated human blood phagocytes by 50%. Furthermore, the scavenging of hydroxyl radicals and singlet oxygen by Cu(I)-thionein was determined, using the 2-deoxyribose fragmentation assay induced by decaying K3CrO8 and the NADPH oxidation caused by UVA illuminated psoralen, respectively. The inhibitory reactivity of Cu-thionein in both assays was compared with that of serum proteins including albumin, ceruloplasmin, transferrin, and ferritin. The galactosamine/endotoxin-induced hepatitis in male NMRI mice was used to evaluate the antiinflammatory reactivity of Cu-thionein in vivo. The serum copper, superoxide dismutase, and sorbitol dehydrogenase concentrations, as well as the activity of polymorphonuclear leukocytes in unseparated blood seemed most appropriate to quantify the protective capacity of Cu-thionein in the course of an oxidative stress-dependent liver injury. The intraperitoneal application of 32.5 mumols/kg thionein-Cu limited this damage to 45%.
Miesel
R
R
Physiologisch-Chemisches Institut der Universität Tübingen, Federal Republic of Germany.
Hartmann
H J
HJ
Weser
U
U
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001798:Blood Proteins / Q000494:pharmacology; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy / Q000473:pathology; D005363:Ficusin / Q000378:metabolism / Q000528:radiation effects; D005609:Free Radicals; D007249:Inflammation; D007274:Injections, Intraperitoneal; D007064:L-Iditol 2-Dehydrogenase / Q000378:metabolism; D008297:Male; D008668:Metallothionein / Q000494:pharmacology*; D051379:Mice; D009249:NADP / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects; D026082:Singlet Oxygen; D013482:Superoxide Dismutase / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014466:Ultraviolet Rays
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001798:Blood Proteins; D005609:Free Radicals; C007121:copper thionein; D026082:Singlet Oxygen; D009249:NADP; D008668:Metallothionein; D007064:L-Iditol 2-Dehydrogenase; D013482:Superoxide Dismutase; D005363:Ficusin; D013755:Tetradecanoylphorbol Acetate; D010100:Oxygen