Metformin Effect Against Rotenone-Induced Parkinsonism-Like Symptoms in a Mouse Model

Israa Hussein Al-Mammory; Ghaith Ali Jasim; Wassan Abdulkareem Abbas

doi:10.54133/ajms.v8i2.1728

Authors

Israa Hussein Al-Mammory Department of Pharmacology and Toxicology, College of Pharmacy, Mustansiriyah University, Baghdad, Iraq
Ghaith Ali Jasim Department of Pharmacology and Toxicology, Faculty of Pharmacy, Al-Bayan University, Baghdad, Iraq
Wassan Abdulkareem Abbas Department of Clinical Lab Sciences, College of Pharmacy, Mustansiriyah University, Baghdad, Iraq

DOI:

https://doi.org/10.54133/ajms.v8i2.1728

Keywords:

α-Synuclein, Dopa decarboxylase, Metformin, Parkinson’s disease, Rotenone, TNF-α

Abstract

Background: Targeting problems in lipid metabolism for the treatment of Parkinson's disease (PD) has advanced significantly in recent years through the use of medications like metformin (MET). In a mouse model of rotenone-induced PD, MET, a commonly prescribed antidiabetic medication, may have a neuroprotective effect. Rotenone is an inhibitor of mitochondrial complex I that can lead to PD and dopaminergic (DA) cell loss. Objective: To evaluate the mechanisms behind the MET neuroprotective effect and possible additive benefits of MET/levodopa-carbidopa (L-DOPA/carbidopa) in rotenone-induced parkinsonism in male mice. Methods: Albino mice were given rotenone (1 mg/kg/48hr, subcutaneous) for 17 days. Following the administration of rotenone, a 30-day oral MET treatment (500 mg/kg/day) was initiated. The neuroprotective effect of MET on rotenone-induced dopaminergic toxicity was assessed by detection of α-synuclein and the neuroinflammatory marker tumor necrosis factor-α (TNF-α), and we also showed that DOPA decarboxylase (DDC) levels in plasma could detect PD using enzyme-linked immunosorbent assay (ELISA) kits. The behavioral tests were performed by wire hanging, catalepsy, and pole tests. Results: Metformin ameliorated the behavioral deficits in the Parkinsonian mouse model, significantly decreased the levels of α-synuclein and tumor necrosis factor-α (TNF-α), and serum DDC levels were significantly reduced. Conclusions: Metformin can alleviate rotenone-induced Parkinson's-like symptoms in a mouse model.

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