Neuroprotective Effect of Dacryodes edulis Ethanolic Leaf Extract on the Hippocampus of Rats of Ketamine-Induced Neurotoxicity

Abstract

Introduction: The brain is an organ that is responsible for knowledge acquisition, cognition and control of body movements. Its normal functioning and structure can be affected by exposure to drugs of abuse (for example ketamine) which can cause disorder in the nervous system. Medicinal plants such as Dacryodes edulis (African pear) have been used overtime to treat or manage neurological disorders and this is due to its rich medicinal qualities. Aim: The aim of this study was to investigate the neuroprotective effect of Dacryodes edulis ethanolic leaf extract on the hippocampus of rats of ketamine-induced neurotoxicity. The objectives were to determine its effects on the cytoachitecture, immuno-histochemistry of the hippocampus, as well as oxidative stress in the rats. Methods: Forty-six (46) rats were procured for this research. Sixteen (16) rats were used for acute toxicity test of the extract, while thirty rats were distributed into five groups comprising of six rats each. The control group was designated as group A and given food and water only, while the ketamine control group (group B) was administered with 100 mg/kg body weight “BW” of ketamine. Groups C, D and E were given ketamine (100 mg/kg BW) + diazepam (0.3 mg/kg BW), ketamine (100 mg/kg BW) + 500 mg/kg BW Dacryodes edulis ethanolic leaf extract and ketamine (100 mg/kg BW) + 1000 mg/kg BW Dacryodes edulis ethanolic leaf extract respectively for 28 days. The ketamine and diazepam were administered intraperitoneally, while the leaf extract was administered with the aid of an oro-gastric tube. The histological and immuno-histochemical studies of the hippocampus, as well as markers of oxidative stress were determined thereafter. Results: The histological result revealed degenerative characteristics in groups B (treated with 100 mg/kg BW ketamine) and C (treated with 100 mg/kg BW ketamine and 0.3 mg/kg BW diazepam). The Dacryodes edulis leaf extract at high dose (group E) was able to ameliorate the neurodegeneration in the hippocampus caused by ketamine overdose, although the ameliorative effects were milder in group D (the lower dose extract group). Furthermore, the immuno-histochemical study showed that the extract was able to maintain the hippocampal neuronal structural integrity. The leaf extract was also able to reduce the lipid peroxidation caused by ketamine as indicated by serum malondialdehyde and glutathione levels. Diazepam was not able to ameliorate the degenerative effects in the various parameters. The result therefore indicates ameliorative potential of the leaf extract but mostly in the high dose group. Conclusion: The leaf extract of Dacryodes edulis can be considered as an alternative neuroprotective drug.