Nauclea latifolia (Rubiaceae) Stem-bark Hydromethanolic Extract Abrogates a Histone Deacetylase Inhibitor - Induced Multifocal Toxicity in Albino Rats

Abstract

Objective: Nauclea latifolia (Rubiaceae) stem-bark enjoys wide patronage in ethnomedicine due to multiplicity of usage. Acute and subacute hematological and biochemical toxicity studies are available in literature but none underpins its ameliorative effect with a histone deacetylase inhibitor (HDAC), valproic acid (VPA) which mediates multifocal toxicity in different histological milieu. Methods: Subacute exposure of experimental albino rats with a high dose of valproic acid (500 mg/kg) was executed orally one hour before post-treatment with Nauclea latifolia stem-bark (NLS) extract in three doses (50, 100, 200 mg/kg) and with another group of rats with reference drug, vinpocetine, 25 mg/kg daily for 28 consecutive days after which hematological and biochemical analyses were executed.  The liver, kidney and lungs were abstracted for histopathological evaluation. Results: The HDAC inhibitor, Valproic acids induced multifocal biochemical insults on liver function enzymes, lipid profiles, electrolytes and kidney function which were dose- dependently and significantly (P < 0.05 – 0.001) abrogated by the varying doses of administered NLS extract. On the histology the NLS extract effects corroborated the biochemical study in the liver and kidney. The NLS did not demonstrate significant toxicological impingement on the hematology and did not alter VPA-induced histomorphological injury in the lungs cytoarchitecture. The reference drug, vinpocetine was unresponsive to VPA-induced alteration in all the tissues investigated in the administered posology. Conclusion: The NLS extract was effective in abrogating toxicological insults in the liver and kidney but not in the lungs. Further studies are required to understand the mechanism of pharmacological effects of NLS extract and the differential in tissue response.