Abstract
Background: 3-Nitropropionic acid (3-NPA), a toxin of fungal origin irreversibly inhibits mitochondrial succinate dehydrogenase (SDH) causing selective degeneration of striatal neurons. There have been studies on the effects of 3-NPA and modulation using various phytochemicals and other molecules on striatum, but there is a lacunae of information regarding the response of other brain regions viz., cortex, cerebellum and hippocampus. Hence the current study is centered on the effect of 3-NPA exposure on the mitochondria of these brain regions. Methods: There were 4 groups: Group IControl; Group II- Bacopa monnieri alone (BM); Group III-3-NPA (ip 75mg/kg bw/ 2days) and sacrificed 24 hrs after the last injection; Group IV-pretreated with 3-NPA for 10 days and later injected with 3-NPA.Various biochemical parameters related to oxidative stress and mitochondrial dysfunctions were carried out. Results: We observed an increase in Oxidative stress (OS) markers in mitochondria of all regions studied in 3-NPA group, where as there was no appreciable damage in prophylaxis group. There was a decrease in reduced glutathione (GSH), total thiols and non-protein thiols in 3- NPA group which was not observed in prophylaxis group. The alterations in antioxidant enzymes observed in 3-NPA group were normalized in prophylaxis group. Further the alterations in mitochondrial functional enzymes, mitochondrial Electron Transport Chain enzymes, Thioredoxin reductase, Na+K+ ATP ase, mitochondrial swelling and mitochondrial reductase activity (MTT) were normalized to various degrees in the BM pretreated group. Conclusion: The study validates the potency of BM extract to mitigate oxidative stress related alterations and mitochondrial dysfunctions induced by 3-NPA.
Keywords: Bacopa monnieri, mitochondrial oxidative stress, 3-NPA, oxidative dysfunctions, prepubertal mice, prophylaxis.
Graphical Abstract
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