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Dabigatran Combined With Benztropine Ameliorates Cobalt Chloride-Induced Parkinsonism in Rats, Restores Protease-Activated Receptor 1 (PAR1), and Mitigates Oxidative Stress

  • 0Department of Medical Pharmacology, Faculty of Medicine Kasr Al-Ainy, Cairo University, Cairo, EGY.
Cureus +

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April 14, 2025

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April 14, 2025

View abstract on PubMed

Summary

This summary is machine-generated.

Dabigatran etexilate combined with benztropine mesylate shows therapeutic potential for cobalt chloride-induced parkinsonism. This combination effectively restored motor functions and neurochemical imbalances, suggesting a role for thrombin inhibition and oxidative stress management.

Area Of Science

  • Neuroscience
  • Pharmacology
  • Toxicology

Background

  • Parkinsonism is linked to thromboembolic and oxidative stress pathways.
  • Cobalt chloride (CoCl2)-induced parkinsonism (CIP) serves as a model for industrial toxin-related health issues.
  • Dabigatran etexilate (DE), an anticoagulant, was explored for its potential as a thrombin inhibitor in this model.

Purpose Of The Study

  • To investigate the therapeutic potential of dabigatran etexilate (DE) in a cobalt chloride (CoCl2)-induced parkinsonism (CIP) model.
  • To evaluate the combined effects of DE and benztropine mesylate (BM) on motor deficits and neurochemical alterations in CIP.
  • To explore the roles of thrombin pathways and oxidative stress in parkinsonism.

Main Methods

  • Rats were administered oral CoCl2 daily for 60 days to induce parkinsonism.
  • Benztropine mesylate (BM) and/or DE were administered from day 31.
  • Evaluated motor behaviors (rearing, postural instability, feeding), performed histopathology of the substantia nigra (SN) and striatum (STR), and assessed levels of dopamine receptors (D2, A1, A2A), PAR1, dopamine (DA), endothelin 1 (ET1), malondialdehyde (MDA), and glutathione (GSH).

Main Results

  • The combination of BM and DE significantly restored rearing, postural stability, and fine motor skills (pasta handling) compared to the CIP model.
  • BM+DE treatment normalized dopamine (DA) levels and dopamine receptor 2 (D2) expression, outperforming DE alone in D2 restoration.
  • BM+DE superiorly restored adenosine receptors (A1, A2A), PAR1, and ET1 levels, while also significantly reducing MDA and increasing GSH, indicating reduced oxidative stress and preserved SN neurons.

Conclusions

  • Combined treatment with benztropine mesylate (BM) and dabigatran etexilate (DE) demonstrates significant therapeutic potential for parkinsonism induced by chronic cobalt chloride exposure.
  • The findings suggest that thrombin-related factors and oxidative stress play crucial roles in modulating the dopaminergic-adenosinergic pathways implicated in parkinsonism.
  • This study highlights a potential therapeutic strategy targeting both thromboembolic and oxidative stress pathways for managing parkinsonism.

Keywords:

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