Ameliorating effect of selenium nanoparticles on cyclophosphamide-induced hippocampal neurotoxicity in male rats: light, electron microscopic and immunohistochemical study

Abstract

BACKGROUND: Cyclophosphamide (CPH) is a widely used chemotherapeutic drug that can affect the hippocampal neurocytes with a subsequent effect on memory and cognitive functions. Nanomedicine has the potential to overcome the current chemotherapeutic side effects, because of the unique nanoscale size and distinctive bioeffects of nanomaterials. So, the present study aims to investigate the potential ameliorative effect of the biologically synthesized nano-selenium (nano-Se) on CPH induced hippocampal neurotoxicity. MATERIALS AND METHODS: Twenty four rats were randomly classified into four groups of 6 rats each: control group, nano-Se group (dose of 0.5 mg biological nano-Se/kg daily via oral gavage), CPH group (dose of 20 mg CPH/kg daily intraperitoneally), and CPH plus nano-Se group. After 4 weeks, the rats were sacrificed and the hippocampus was excised and processed. Sections were stained with haematoxylin and eosin stain and immunohistochemically stained for caspase-3 (apoptosis marker) and glial fibrillary acidic protein (astrocytic activity marker) (GFAP). Morphometric analysis and transmission electron microscopic (TEM) examination were also done. RESULTS: Control and nano-Se groups revealed no structural changes. By light microscopy, CPH group showed degeneration and necrosis of hippocampal neurocytes, significantly reduced thickness of the neurocyte cell layers, increased expression of GFAP and caspase-3 immunostains and significantly elevated apoptotic index. Moreover, neurocytes damage, mitochondrial cristeolysis, mild dilation of rough endoplasmic reticulum, and disrupted neurolemmal sheaths of nerve fibres were also demonstrated by TEM. Nano-Se cotreatment in the fourth group reversed all the aforementioned deleterious changes that induced by CPH in the hippocampal neurocytes. CONCLUSIONS: Treatment with CPH caused damage to hippocampal neurocytes that can be reversed by biological nano-Se co-treatment.