Lipophilic statins (e.g., simvastatin (SMV)) played a cytoprotective role against various injuries via mitigating neuroinflammation and attenuating oxidative damage. Doxorubicin (Dox) leads to tissue injury, particularly cardiotoxicity and brain toxicity. The present study aimed to investigate the neuroprotective potential of SMV against Dox-induced neurotoxicity in rats. A total of 56 Albino Wistar rats were housed in cages and subclassified into control male and female groups, Dox male and female groups, SMV male and female groups, and SMV+Dox male and female groups. The brain tissue samples for all groups were harvested at day 16 and assessed through histological examination. The scoring results of these rats' brain sections indicated that control groups demonstrated normal histology (scoring 0), SMV groups associated with mild congestion in both sexes; mild demyelination only in females (scoring 1), Dox group demonstrated severe histopathology (scoring 3), and the combination of SMV+Dox demonstrated a notable reduction in histopathology scoring (Scores 0-1). The outcomes of the present study provided clear evidence that SMV provided marked neuroprotection against Dox-induced neurotoxicity in both male and female rats.
