Molecular and biochemical aspects of the neuroprotective effect of the selective estrogen receptor modulator tamoxifen in a model of acute cerebral ischemia

Abstract

We studied the neurochemical aspects of the neuroprotective action of a selective modulator of the estrogen receptors, tamoxifen citrate, in a model of acute cerebral ischemia (ACI). It was shown that modeling of cerebral ischemia is followed by pathobiochemical changes in the brain tissue: a rapid shift of thioldisulfide homeostasis, intensification of free radical oxidation, and impaired synthesis of the cytoprotective protein Hsp70. A course of the 1 mg/kg tamoxifen citrate led to the normalization of the thiol-disulfide system due to an increase of the glutathione level in the brain tissue which, in turn, restricted the development of oxidative and nitrosative stress. In addition, Western blot analysis showed that treatment with tamoxifen citrate increased the Hsp70 level in the brain tissue, which resulted from genomic and non-genomic actions. The neuroprotective profile of tamoxifen citrate that we found here opens the future perspective of the studies in this field for introduction of this agent as a neuroprotective drug into clinical practice.