Haematological Alterations Induced by Valproic Acid and the Protective Role of Nano Formulation in Male Rabbits

Abstract

Valproic acid (VPA) is a widely prescribed antiepileptic drug whose long-term use is frequently associated with haematological toxicity. The present study aimed to evaluate the haematological alterations induced by valproic acid and to investigate the protective potential of a synthesised nano-co-polymer formulation in male rabbits. The nano-co-polymer was prepared via an esterification process and structurally characterised using FT-IR and ^1H-NMR spectroscopy, which confirmed successful ester bond formation and aromatic substitutions. Twenty male rabbits were randomly allocated into four groups (n = 5): a control group, a VPA-treated group (200 mg/kg), a nano-formulation group (100 mg/kg), and a combined VPA + nano-formulation group, treated for six weeks. Haematological parameters, including haemoglobin (Hb), red blood cells (RBC), white blood cells (WBC), hematocrit (HCT), platelets (PLT), and red cell indices (MCV, MCH, MCHC), were assessed using an automated haematology analyser. VPA administration significantly reduced haemoglobin concentration (11.5 ± 0.23 g/dL) compared with the control group (13.4 ± 0.28 g/dL, P < 0.05), accompanied by a significant decrease in WBC count (7.9 ± 0.31 ×10³/µL versus 8.83 ± 0.26 ×10³/µL). A concomitant reduction in hematocrit was also observed (37.33 ± 0.71 vs. 40.27 ± 0.25), indicating mild anaemia and immunosuppression. In contrast, rabbits treated with the nano formulation alone showed haematological values comparable to, or slightly higher than, controls, particularly WBC count (9.4 ± 0.39 ×10³/µL). Notably, co-administration of the nano formulation with VPA significantly ameliorated VPA-induced haematological disturbances, restoring Hb, WBC, and HCT levels toward normal ranges. No significant alterations were observed in RBC count, platelet count, or red cell indices among the experimental groups. In conclusion, valproic acid induces mild but significant haematological toxicity in male rabbits, mainly affecting haemoglobin and leukocyte levels. The synthesised nano-co-polymer formulation demonstrated a clear protective effect, attenuating VPA-induced haematological alterations. These findings highlight the potential of nano-based formulations as supportive therapeutic strategies to reduce drug-induced hematotoxicity and enhance treatment safety.