Ebselen reversed peripheral oxidative stress induced by a mouse model of sporadic Alzheimer's disease.

Abstract

Intracerebroventricular streptozotocin injection (icv STZ) is a well established sporadic Alzheimer's disease (AD) model in rodents. AD is characterized by neuronal degeneration accompanied by central oxidative stress. Studies also indicate peripheral oxidative damage in AD, but if the icv STZ model of sporadic AD mimics this feature is an open question. This study aimed to investigate if icv STZ administration induces peripheral oxidative stress and the antioxidant action of Ebselen, compared to the reference drug (donepezil), in this sporadic AD model. Male adult Swiss mice received icv STZ (days 1 and 3). Mice received Ebselen (10mg/kg, i.p) or Donepezil (5mg/kg, i.p) for 14days. Mice were killed and the kidney and liver were excised to determine parameters of oxidative stress and toxicity markers. The mice icv STZ-injected showed peripheral oxidative stress. Ebselen reversed renal lipid peroxidation in the icv STZ administered mice by modulating NPSH levels, SOD and CAT activities, whereas Donepezil, modulated only NPSH levels. Ebselen and Donepezil counteracted hepatic lipid peroxidation in STZ-injected mice by modulating NPSH levels and CAT activity. The δ-ALA-D activity was inhibited in the kidney, but not in the liver, whereas the icv STZ-injected mice had an increase in the GST activity in both tissues. Ebselen reversed the increase in the hepatic GST activity of the STZ-injected mice. Donepezil increased renal GST activity in the control mice. In conclusion, this study demonstrates that the icv STZ administration induced peripheral oxidative stress. Ebselen, similar to Donepezil, was effective against peripheral oxidative stress in a mouse model of sporadic AD.