Hesperetin protects against rotenone-induced motor disability and neurotoxicity via the regulation of SIRT1/NLRP3 signaling.
Toxicol Mech Methods
; 34(9): 1045-1060, 2024 Nov.
Article
in En
| MEDLINE
| ID: mdl-39119966
ABSTRACT
Rotenone is a pesticide that causes complex I inhibition and is widely known to induce motor disability and experimental Parkinson's disease (PD) in rodents. Evidence suggests a crucial role for sirtuin/nuclear factor-kappaB/nod-like receptor family, pyrin domain-containing 3 (SIRT1/NFκB/NLRP3) signaling and inflammation in PD and rotenone neurotoxicity. Hesperetin (C16H14O6) is a citrus flavonoid with documented anti-inflammatory activity. We investigated the value of hesperetin in delaying rotenone-induced PD in mice and the possible modulation of inflammatory burden. PD was induced in mice via rotenone injections. Groups were assigned as a vehicle, PD, or PD + hesperetin (50 or 100 mg/kg) and compared for the motor function, protein level (by ELISA), and gene expression (by real-time PCR) of the target proteins, histopathology, and immunohistochemistry for tyrosine hydroxylase enzyme. Hesperetin (50 or 100 mg/kg) alleviated the motor disability and the striatal dopamine level and decreased the expression of NLRP3 and NF-κB but increased SIRT1 expression (p < 0.05). Further, it enhanced the neural viability and significantly decreased neural degeneration in the substantia nigra, hippocampus, and cerebral cortex (p < 0.05). Taken together, we propose that hesperetin mediates its neuroprotective function via alleviating modulation of the SIRT1/NFκB/NLRP3 pathway. Therefore, hesperetin might delay the PD progression.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Rotenone
/
Signal Transduction
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Neuroprotective Agents
/
Sirtuin 1
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NLR Family, Pyrin Domain-Containing 3 Protein
/
Hesperidin
Limits:
Animals
Language:
En
Journal:
Toxicol Mech Methods
Journal subject:
TOXICOLOGIA
Year:
2024
Document type:
Article
Affiliation country:
Egipto
Country of publication:
Reino Unido