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Ameliorative effects of oleanolic acid on fluoride induced metabolic and oxidative dysfunctions in rat brain:
Chaitali Sarkar1, Sudipta Pal1, Niranjan Das2
1Nutritional Biochemistry Laboratory, Department of Human Physiology, Tripura University, Suryamaninagar 799 022, West Tripura, India.
Abstract:
Beneficial effects of oleanolic acid on fluoride-induced oxidative stress and certain metabolic dysfunctions were studied in four regions of rat brain. Male Wistar rats were treated with sodium fluoride at a dose of 20 mg/kg b.w./day (orally) for 30 days. Results indicate marked reduction in acidic, basic and neutral protein contents due to fluoride toxicity in cerebrum, cerebellum, pons and medulla. DNA, RNA contents significantly decreased in those regions after fluoride exposure. Activities of proteolytic enzymes (such as cathepsin, trypsin and pronase) were inhibited by fluoride, whereas transaminase enzyme (GOT and GPT) activities increased significantly in brain tissue. Fluoride appreciably elevated brain malondialdehyde level, free amino acid nitrogen, NO content and free OH radical generation. Additionally, fluoride perturbed GSH content and markedly reduced SOD, GPx, GR and CAT activities in brain tissues. Oral supplementation of oleanolic acid (a plant triterpenoid), at a dose of 5mg/kgb.w./day for last 14 days of fluoride treatment appreciably ameliorated fluoride-induced alteration of brain metabolic functions. Appreciable counteractive effects of oleanolic acid against fluoride-induced changes in protein and nucleic acid contents, proteolytic enzyme activities and other oxidative stress parameters indicate that oleanolic acid has potential antioxidative effects against fluoride-induced oxidative brain damage.
Insights
Oleanolic acid, a plant triterpenoid, counteracts fluoride-induced brain damage by reducing oxidative stress and restoring metabolic functions. This study highlights its potential as a neuroprotective agent against fluoride toxicity.
Area of Science:
- Neuroscience
- Biochemistry
- Toxicology
Background:
- Fluoride exposure can induce oxidative stress and metabolic dysfunction in the brain.
- Specific brain regions like the cerebrum, cerebellum, pons, and medulla are susceptible to fluoride toxicity.
- Oleanolic acid is a plant-derived triterpenoid with potential therapeutic properties.
Purpose of the Study:
- To investigate the protective effects of oleanolic acid against fluoride-induced oxidative stress and metabolic alterations in the rat brain.
- To evaluate the impact of oleanolic acid supplementation on key biochemical parameters in different brain regions exposed to sodium fluoride.
Main Methods:
- Male Wistar rats were administered sodium fluoride (20 mg/kg b.w./day) for 30 days.
- Oleanolic acid (5 mg/kg b.w./day) was given orally during the last 14 days of fluoride treatment.
- Biochemical analyses were performed on brain tissues to assess protein, nucleic acid, enzyme activities, and oxidative stress markers.
Main Results:
- Fluoride exposure significantly reduced protein and nucleic acid content, inhibited proteolytic enzymes, and increased transaminase activities in brain regions.
- Fluoride elevated malondialdehyde, free amino acid nitrogen, nitric oxide, and free hydroxyl radical levels, while depleting glutathione and reducing antioxidant enzyme activities (SOD, GPx, GR, CAT).
- Oleanolic acid supplementation ameliorated these fluoride-induced biochemical and oxidative changes, indicating a neuroprotective effect.
Conclusions:
- Oleanolic acid demonstrates significant antioxidative effects against fluoride-induced oxidative brain damage.
- It effectively counteracts fluoride-induced alterations in brain metabolic functions, including protein/nucleic acid levels and enzyme activities.
- Oleanolic acid shows promise as a therapeutic agent for mitigating fluoride neurotoxicity.
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