Type 2 diabetes induced oxidative brain injury involves altered cerebellar neuronal integrity and elemental distribution, and exacerbated Nrf2 expression: therapeutic potential of raffia palm (Raphia hookeri) wine

Abstract

Neurodegenerative diseases, such as Alzheimer’s disease have been recognized as one of the microvascular complications of type 2 diabetes (T2D). In this study, the effect of T2D on neuronal integrity and elemental distribution in the cerebellar cortex, as well as the therapeutic effect of Raffia Palm (Raphia hookeri) wine (RPW) were investigated in male albino rats. T2D was induced in 4 groups of rats using fructose and streptozotocin. One group served as negative control which was administered water, the second and third group were administered 150 and 300 mg/kg bodyweight of RPW, while the fourth was administered metformin (200 mg/kg bodyweight). Two other groups of normal rats were administered distilled water (control) and of RPW (300 mg/kg bodyweight). The rats were sacrificed after 5 weeks of treatment, and brains were collected. The cerebellum was removed, and several parts analyzed by immunochemistry, histology and scanning electron microscopy (SEM). Remaining brain tissues were used to analyze for the oxidative stress biomarkers and acetylcholinesterase activity. These analyses revealed oxidative damage with concomitantly increased acetylcholinesterase activity and upregulation of Nrf2 expression in the diabetic brain cerebellar cortexes. Histological and microscopic analysis also revealed altered distribution of neurons and axonal nodes with concomitant elevated levels of several heavy metals. Treatment with RPW significantly elevated glutathione (GSH) level, superoxide dismutase (SOD) and catalase activities, as well as depleted acetylcholinesterase and malondialdehyde (MDA) level and concomitantly inhibited Nrf2 expression. It also improved neuronal integrity and reduced the levels of heavy metals in brain. Taken together, the results of this study suggest that the RPW may afford a novel neuroprotective potential against diabetic neurodegeneration.