Glutamate excitotoxicity induced by orally administered propionic acid, a short chain fatty acid can be ameliorated by bee pollen

Abstract

Background: Rodent models may guide investigations towards identifying either environmental neuro-toxicants or drugs with neuro-therapeutic effects. This work aims to study the therapeutic effects of bee pollen on brain glutamate excitotoxicity and the impaired glutamine-glutamate- gamma amino butyric acid (GABA) circuit induced by propionic acid (PPA), a short chain fatty acid, in rat pups.

Methods: Twenty-four young male Western Albino rats 3-4 weeks of age, and 45-60 g body weight were enrolled in the present study. They were grouped into four equal groups: Group 1, the control received phosphate buffered saline at the same time of PPA adminstration; Group 2, received 750 mg/kg body weight divided into 3 equal daily doses and served as acute neurotoxic dose of PPA; Group 3, received 750 mg/kg body weight divided in 10 equal doses of 75 mg/kg body weight/day, and served as the sub-acute group; and Group 4, the therapeutic group, was treated with bee pollen (50 mg/kg body weight) for 30 days after acute PPA intoxication. GABA, glutamate and glutamine were measured in the brain homogenates of the four groups.

Results: The results showed that PPA caused multiple signs of excitotoxicity, as measured by the elevation of glutamate and the glutamate/glutamine ratio and the decrease of GABA, glutamine and the GABA/glutamate ratio. Bee pollen was effective in counteracting the neurotoxic effects of PPA to a certain extent.

Conclusion: In conclusion, bee pollen demonstrates ameliorating effects on glutamate excitotoxicity and the impaired glutamine-glutamate-GABA circuit as two etiological mechanisms in PPA-induced neurotoxicity.

Keywords: Bee pollen; GABA; Glutamate excitotoxicity; Glutamine; Propionic acid.

Fig. 1

Schematic presentation of the experimental work demonstrating, dosage, duration of different studied groups

Fig. 2

Mean ± S.D. and error bars of all parameters in all groups

Fig. 3

Percentage increase or decrease of the measured parameters relative to controls, diagrammatically presented as 100%

Fig. 4

Positive and negative Pearson’s correlations between the measured parameters with a best fit line curve

Fig. 5

ROC curves of all parameters in PPA-chronic, PPA-acute or PPA-acute-followed with pollen as a treatment for glutamate neurotoxicity