Novel Nickel Superoxide Dismutase Treatment Delays FeCl3‐induced Arterial Thrombosis in Rats

Abstract

Nickel complexes, [Ni(H2BA(R)TPP)](ClO4)2 (R = Ph for 1 or iPr for 2), supported by a pentadentate ligand H2BA(R)TPP were synthesized to mimic the nickel superoxide dismutase (NiSOD). Diabetes may exacerbate oxidative stress‐induced thrombosis. We explored the antioxidant activity and its biomedical effects of the synthetic NiSOD in the FeCl3‐induced carotid arterial thrombosis in the type I diabetic rats.We determined the scavenging reactive oxygen species responses in vitro by a chemiluminescent amplification method. Female Wistar rats in vivo were used and divided into four groups: control rats, streptozotocin (STZ, 60 mg/kg) treated rats, control rats with NiSOD (10 μg/ml), and STZ rats with NiSOD treatment. We investigated the underlying mechanisms of NiSOD on arterial thrombosis by immunohistochemistry and western blotting.Our data showed that NiSOD dose‐dependently decreased O2‐. and H2O2. The FeCl3‐induced time to occlusion of the carotid artery was 21±5 min in control rats, 21±2 min in STZ rats, 24±4 min in control rats with NiSOD treatment and 28±6 min in STZ rats with NiSOD (10 μg/ml), respectively. By western blot and immunohistochemistry, FeCl3 increased reactive oxygen species production, chemokine (C‐X3‐C motif) ligand 1 (CX3CL1), intercellular adhesion molecule 1 (ICAM‐1), vascular cell adhesion molecule‐1 (VCAM‐1), 4‐hydroxynonenal (4‐HNE) and 3‐nitrotyrosine (3‐NT) expression in the damaged arterial endothelium. NiSOD treatment significantly depressed the level of reactive oxygen species, CX3CLl, ICAM‐1, VCAM‐1, 4‐HNE and 3‐NT in the endothelial areas of control and STZ rats.These data suggest that a synthesized NiSOD can protect oxidative stress‐induced arterial thrombosis through the actions of antioxidant, anti‐adhesion, anti‐inflammation.