Thymoquinone-loaded solid lipid nanoparticles mitigate 3-Nitropropionic acid-induced mitochondrial dysfunction and...

Area of Science:

• Neuroscience
• Biochemistry
• Pharmacology

Background:

• 3-Nitropropionic acid (3-NP) induces neurotoxicity by damaging mitochondria and mimicking Huntington's disease (HD) pathology.
• 3-NP-induced neuronal death involves mitochondrial dysfunction, altered gene expression, and weakened antioxidant systems.

Purpose of the Study:

• To investigate the neuroprotective effects of thymoquinone encapsulated in solid lipid nanoparticles (NanoTQ) against 3-NP-induced neurotoxicity.
• To evaluate NanoTQ's impact on mitochondrial biogenesis, neurotrophic factors, and antioxidant pathways in the rat striatum.

Main Methods:

• Rats were administered 3-NP (10 mg/kg) for 14 days to induce neurotoxicity.
• NanoTQ (10 and 20 mg/kg) and thymoquinone (TQ) (40 and 80 mg/kg) treatments were administered.
• Mitochondrial function, protein expression (PGC-1α, p-CREB, TORC1, SIRT1, PPARγ, BDNF, GDNF, Nrf-2, HO-1, Keap1), and membrane permeability were assessed.

Main Results:

• 3-NP inhibited mitochondrial complex enzymes and increased membrane permeability.
• NanoTQ treatment significantly restored mitochondrial complex enzyme activity and PGC-1α mediated mitochondrial biogenesis.
• NanoTQ upregulated neurotrophic factors (BDNF, GDNF) and enhanced antioxidant defenses (Nrf-2, HO-1) while reducing Keap1.

Conclusions:

• NanoTQ effectively mitigates 3-NP-induced neurotoxicity in rats.
• The protective effects are attributed to the regulation of mitochondrial biogenesis, neurotrophic signaling, and antioxidant systems.
• NanoTQ demonstrates potential as a therapeutic agent for Huntington's disease-like pathology.