Unravelling Tamoxifen’s Neuroprotective Effects against Manganese-Induced Neurodegeneration, Cognitive Impairment and Hippocampal Damage Via the Nrf-2 Pathway in Adult Male Wistar Rats

Abstract

Aims: Neurodegenerative diseases pose a serious threat to public health. Manganese (Mn) is a metal necessary for biological systems; however, it can become hazardous at high concentrations, causing neurological damage. This study explores tamoxifen's potential to protect against Mn-induced neurotoxicity in adult male Wistar rats. Methodology: Forty (40) adult male Wistar Rats weighing between 170g-220g were used and divided into four groups (A-D) (n=10). Manganese (Mn) and Tamoxifen (TMX) dosages were prepared and administered daily for 45 days through oral gavage. Group A received normal saline as a placebo; Group B received 200 mg/kgbwt of Mn only; Group C received 100 mg/kgbwt of TMX and 200 mg/kgbwt of Mn; Group D received 100 mg/kgbwt of TMX only. At the end of the experiment, behavioral tests were carried out, and animals were sacrificed; the brain was then excised, cleaned, and washed with saline for analysis.  Results: After the 45 days of treatment the Mn-only group exhibited clear signs of neurobehavioral toxicity. On the other hand, the TMX-treated rats exhibited significantly improved exploratory behavior and locomotor activity indicating its effect in reverting Mn neurotoxicity. The histological assessments further revealed that TMX preserved hippocampal morphology, reducing glial cell distortion and vacuolation caused by Mn exposure, while the immunohistochemical analysis showed activated Nrf-2 expression in TMX-treated groups. Conclusion: These results suggest that TMX has significant neuroprotective effects and could be a potential therapeutic agent for neurodegenerative diseases.