Association of zinc administration with growth suppression of intracranial aneurysms via induction of A20

Abstract

OBJECTIVE Zinc is an essential micronutrient with multiple biological effects, including antiinflammation. Previously, the authors demonstrated that the pathogenesis of intracranial aneurysms (IAs) is strongly related to chronic inflammation. In this study, the authors investigated whether administration of zinc inhibits the growth of IAs in a rat model. METHODS The authors analyzed surgically induced IAs in Sprague-Dawley male rats, which were subsequently treated with intraperitoneal injections of zinc sulfate heptahydrate (ZnSO4; 3 mg/kg/day) or vehicle for 4 weeks. RESULTS Size and wall thickness ratios of experimentally induced IAs were assessed in both treatment groups after induction and in a control group. The effects of zinc administration in IAs were examined by immunohistochemistry and Western blotting. Zinc administration significantly suppressed aneurysm size and also preserved the internal elastic lumen. Administration of zinc significantly attenuated infiltration of macrophages into IAs. CONCLUSIONS Zinc treatment significantly increased expression of the antiinflammatory signaling protein A20, an inhibitor of the nuclear factor κB (NF-κB) pathway, in rat IAs. Zinc administration may prevent the growth of rat IAs by inducing A20-attributed inactivation of NF-κB signaling.