Abstract
Kolaviron is a phytochemical isolated from Garcina kola (G. kola); a common oral masticatory agent in Nigeria (West Africa). It is a bioflavonoid used - as an antiviral, anti-inflammatory and antioxidant - in relieving the symptoms of several diseases and infections. In this study we have evaluated the neuroprotective and regenerative effect of kolaviron in neurons of the prefrontal cortex (Pfc) before or after exposure to sodium azide (NaN3) induced oxidative stress. Separate groups of animals were treated as follows; kolaviron (200 mg/Kg) for 21 days; kolaviron (200 mg/Kg for 21 days) followed by NaN3 treatment (20 mg/Kg for 5 days); NaN3 treatment (20 mg/Kg for 5 days) followed by kolaviron (200 mg/Kg for 21 days); 1 ml of corn-oil (21 days-vehicle); NaN3 treatment (20 mg/Kg for 5 days). Exploratory activity associated with Pfc function was assessed in the open field test (OFT) following which the microscopic anatomy of the prefrontal cortex was examined in histology (Haematoxylin and Eosin) and antigen retrieval Immunohistochemistry to show astroglia activation (GFAP), neuronal metabolism (NSE), cytoskeleton (NF) and cell cycle dysregulation (p53). Subsequently, we quantified the level of Glucose-6-phosphate dehydrogenase (G6PDH) and lactate dehydrogenase (LDH) in the brain tissue homogenate as a measure of stress-related glucose metabolism. Kolaviron (Kv) and Kolaviron/NaN3 treatment caused no prominent change in astroglia density and size while NaN3 and NaN3/Kv induced astroglia activation and scar formation (astrogliosis) in the Pfc when compared with the control. Similarly, Kolaviron and Kv/NaN3 did not alter NSE expression (glucose metabolism) while NaN3 and NaN3/Kv treatment increased cortical NSE expression; thus indicating stress related metabolism. Further studies on enzymes of glucose metabolism (G6PDH and LDH) showed that NaN3 increased LDH while kolaviron reduced LDH in the brain tissue homogenate (P < 0.001). In addition kolaviron treatment before (P < 0.001) or after (P < 0.05) NaN3 treatment also reduced LDH expression; thus supporting its role in suppression of oxidative stress. Interestingly, NF deposition increased in the Pfc after kolaviron treatment while Kv/NaN3 showed no significant change in NF when compared with the control. In furtherance, NaN3 and NaN3/Kv caused a decrease in NF deposition (degeneration). Ultimately, the protective effect of KV administered prior to NaN3 treatment was confirmed through p53 expression; which was similar to the control. However, NaN3 and NaN3/Kv caused an increase in p53 expression in the Pfc neurons (cell cycle dysregulation). We conclude that kolaviron is not neurotoxic when used at 200 mg/Kg BW. Furthermore, 200 mg/Kg of kolaviron administered prior to NaN3 treatment (Kv/NaN3) was neuroprotective when compared with Kolaviron administered after NaN3 treatment (NaN3/Kv). Some of the observed effects of kolaviron administered before NaN3 treatment includes reduction of astroglia activation, absence of astroglia scars, antioxidation (reduced NSE and LDH), prevention of neurofilament loss and cell cycle regulation.
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Abbreviations
- NaN3 :
-
Sodium azide
- Kv:
-
Kolaviron
- BW:
-
Body weight
- NF:
-
Neurofilament
- NSE:
-
Neuron specific enolase
- GFAP:
-
Glia fibrillary acidic protein
- G6PDH:
-
Glucose-6-phosphate dehydrogenase
- LDH:
-
Lactate dehydrogenase
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Grants
This work is supported by the ISN-CAEN 1A grants awarded by the International Society for Neurochemistry to OJO.
Author contributions
OJO and BUE initiated the research. OBA participated in the design and implementation of the experiments. OMO, OOB and BJL participated in the implementation of the experiment, analysis of results and manuscript writing. OJO, BUE, OOM proof read the article for final corrections.
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The Authors hereby declare there is no conflict of interest associated with this study or any of the procedures and materials used for the purpose of the study.
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Olajide, O.J., Enaibe, B.U., Bankole, O.O. et al. Kolaviron was protective against sodium azide (NaN3) induced oxidative stress in the prefrontal cortex. Metab Brain Dis 31, 25–35 (2016). https://doi.org/10.1007/s11011-015-9674-0
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DOI: https://doi.org/10.1007/s11011-015-9674-0