Hepatoprotective reactivity of a copper-di-Schiffbase active centre analogue of Cu2Zn2 superoxide dismutase.
1. The anti-inflammatory and hepatoprotective efficacy of CuPu(Py)2 ((N,N'-bis(2-pyridyl-methylene)-1,4-butanediamine) (N,N',N",N")-Cu2+), a serum-stable, copper-di-Schiffbase active centre analogue of Cu2Zn2 superoxide dismutase was tested in male NMNR mice suffering from endotoxin/galactosamine-induced hepatitis. 2. Parameters including the activities of serum transaminases and sorbitol-dehydrogenase as well as the levels of reactive oxygen and nitrogen intermediates which were used to quantify the disease activity. 3. A dose-dependent inhibition of hepatic enzyme release was noted in the presence of 0.1-10 mg/kg of CuPu(Py)2. 4. The release of transaminases from damaged liver cells was reduced by 68% and paralleled the reduction of serum levels of nitric oxides. 5. Elevated levels of reactive oxygen species were normalized to those healthy controls. 6. The copper-free apochelate Pu(Py)2, which is unable to dismutate superoxide, did not display any anti-inflammatory reactivity.
Miesel
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Deutsches RheumaForschungsZentrum (German Rheumatology Research Centre), Department of Biochemistry, Berlin, Germany.
Altrichter
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Kurpisz
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D000410:Alanine Transaminase / Q000187:drug effects; D000818:Animals; D000975:Antioxidants; D001219:Aspartate Aminotransferases / Q000187:drug effects; D056486:Chemical and Drug Induced Liver Injury; D003300:Copper / Q000494:pharmacology; D008099:Liver / Q000187:drug effects*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009569:Nitric Oxide / Q000097:blood; D013482:Superoxide Dismutase / Q000494:pharmacology*
D000975:Antioxidants; D009569:Nitric Oxide; D003300:Copper; D013482:Superoxide Dismutase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase