Protective Effects of Daflon Against Haloperidol-Induced Neurobehavioral Alterations, Oxidative Stress, Neuroinflammation, and Cerebellar Histomorphological Changes in Mice

Abstract Background Haloperidol is widely used to manage mental disorders, but its clinical use is limited by its extrapyramidal and neurotoxic side effects. This study investigates the potential of Daflon to attenuate haloperidol-induced neurobehavioral, biochemical, and cerebellar alterations in mice. Method Twenty-five male Swiss mice were randomly divided into five groups (n = 5/group): a saline control group (2 mL/kg), a haloperidol-only group (2 mg/kg), haloperidol plus Daflon groups (50 and 100 mg/kg), and a haloperidol plus levodopa/carbidopa (10 mg/kg) group. Following seven consecutive days of co-treatment, neurobehavioral performance was evaluated using open field and Y-maze tests. Brain tissues were subsequently harvested for histomorphological examination of the cerebellum and brain tissue biochemical assessments of the levels of CAT, SOD, GSH, MDA, TNF-α, and IL-1β. Results The group that received haloperidol alone exhibited significant behavioral impairments (reduced open-field locomotion and Y-maze spontaneous alternation, indicating short-term spatial working memory deficits), depleted antioxidants (CAT, SOD, GSH), and elevated lipid peroxidation (MDA) and proinflammatory markers (TNF-α, IL-1β) alongside localized cerebellar structural distortions. Groups co-treated with Daflon and the standard drug levodopa-carbidopa exhibited significant improvement in motor activity and short-term spatial working memory. This co-treatment also improved the antioxidant levels of CAT, SOD, and GSH, reduced MDA, TNF-α, and IL-1β levels, and preserved target cerebellar histoarchitecture Conclusion These outcomes suggest that Daflon possesses neuroprotective properties against haloperidol-induced neurobehavioral, biochemical, and cerebellar alterations. These therapeutic effects are likely mediated through Daflon's capacity to modulate oxidative stress and neuroinflammatory pathways, highlighting its potential as a promising adjunct therapy to mitigate antipsychotic-induced neurotoxicity.