Hepatoprotective reactivity of a copper-di-Schiffbase active centre analogue of Cu2Zn2 superoxide dismutase

• Published in: General pharmacology 1995-10, Vol.26 (6), p.1261-1266
• Main Authors: Miesel, R, Altrichter, S, Kurpisz, M
• Format: Article
• Language: English
• Subjects: Alanine Transaminase - drug effects; Animals; Antioxidants; Aspartate Aminotransferases - drug effects; Chemical and Drug Induced Liver Injury; Copper - pharmacology; Liver - drug effects; Male; Mice; Mice, Inbred Strains; Nitric Oxide - blood; Superoxide Dismutase - pharmacology
• ISSN: 0306-3623
• DOI: 10.1016/0306-3623(94)00303-5

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.