Endpoint-Dependent Biochemical and Histopathological Effects of Orientin in a Short-Term 3-Nitropropionic Acid Mouse Model

Objective: The objective of this study was to describe the biochemical and histopathological changes associated with orientin co-administration in a short-term 3-nitropropionic acid (3-NPA) mouse model. Methods: Twenty-four adult female Swiss albino mice were allocated to Control, Orientin, 3-NPA, and 3-NPA + Orientin groups (n = 6). Mice received 3-NPA (12.5 mg/kg/day, i.p.) and/or orientin (20 mg/kg/day, i.p.) for seven days. After midsagittal division of the brain, GSH, MDA, SOD, GPx, and CAT were measured in a homogenate prepared from one hemisphere per animal; caspase-3, COX-2, iNOS, and MCP-1 were measured in plasma. The contralateral hemisphere was used for striatal histology and assessment of 8-OHdG, 4-HNE, and GFAP immunoreactivities; right–left allocation was balanced within each group. Results: Factorial analysis identified endpoint-dependent 3-NPA and orientin effects. Relative to 3-NPA alone, co-treatment increased GSH, SOD, and CAT and reduced MDA, caspase-3, and MCP-1. GPx, COX-2, and iNOS did not differ significantly between the 3-NPA and combined-treatment groups. Histopathological injury appeared less extensive with co-treatment. Although 8-OHdG and 4-HNE staining was lower descriptively, the pairwise IRS comparisons between the 3-NPA and combined-treatment groups were not significant; GFAP did not differ among groups. Conclusion: Orientin co-administration was associated with a partial, endpoint-dependent biochemical and histopathological profile. Because behavioral outcomes and direct pathway or target-intervention experiments were not performed, these findings do not establish functional neuroprotection or a specific molecular mechanism.