HEPATOPROTECTIVE REACTIVITY OF A COPPER-DI-SCHIFFBASE ACTIVE-CENTER ANALOG OF CU2ZN2 SUPEROXIDE-DISMUTASE

1. The anti-inflammatory and hepatoprotective efficacy of CuPu(Py)(2) ({[N,N'-bis(2-pyridylmethylene)-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.