Cerebroprotective Effects of Dimeric Copper(II) Bis(o-acetoxybenzoate) on Ischemia-reperfusion Injury in Gerbils

The cerebroprotective effects of copper aspirinate [dimeric copper(II) bis(o-acetoxybenzoate)] were investigated in gerbils subjected to 10-min global cerebral ischemia followed b 60-min reperfusion. The results showed that intragastric copper aspirinate (7.5, 15.0 and 30.0 mg Kg−1 ) markedly promoted the recovery of the electroencephalogram amplitude, attenuated the increase of lipid peroxide content and the decrease of superoxide dismutase activity in the cortex during ischemia-reperfusion injury. It suggested that copper aspirinate possesses potential neuroprotective properties, the mechanism of which might be related to an increase of the activity of endogenous superoxide dismutase.

Inhibitory Effects of Dimeric Copper(II) bis(o-acetoxybenzoate) on Platelet-neutrophil adhesion and Thrombosis

Antithrombotic effect of the copper-aspirin complex (dimeric copper(II) bis(o-acetoxybenzoate) was evaluated in the model of venous thrombosis; its effects on platelet-neutrophil adhesion were investigated by use of rosette assay. The results showed that the intragastrically administered copper-aspirin complex (5, 7, and 10 mg kg−1) dose-dependently lowered the wet and dry thrombus weight; it significantly decreased the binding of arachidonic acid-activated platelets to neutrophils with an IC50 value of 41.5 μmol L-1. The results suggested that copper aspirinate inhibited platelet-neutrophil adhesion and resulted in a more potent antithrombotic activity.

Distribution of Copper in Rats Submitted to Treatment With Copper Aspirinate

The distribution of copper in Sprague – Dawley rats following a three month oral administration of 0,10 or 50mg/kg copper aspirinate has been investigated. Metal content was determined by ICP – AES in blood, brain, kidney, liver, lung, spleen, and dejection. The results show that treatment with copper aspirinate did not cause accumulation of copper in rats and excess ingested copper was excreted through feces.

Potential Application of Copper Aspirinate in Preventing and Treating Thromboembolic Diseases

The efficacy of copper aspirinate against thrombotic diseases has been tested in animal models. The results show that copper aspirinate, following ig pretreatment for 7 days at 0.012mmol/kg markedly prolonged the bleeding time and inhibited the mortality induced by arachidonic acid (AA) in mice. On cereral ischemia model pretreatment with 0.018mmol/kg copper aspirinate ig significantly increased survival of animals and the density of intact hippocampal CA1 cells and decreased brain calcium concentration. Its anticerebral ischemia activity was superior to or equal to nimodipine. It is, therefore, suggested that copper aspirinate is very promising in becoming an antithrombotic drug in preventing and treating thrombotic diseases.