Effectiveness of Fragment C Domain of Tetanus Toxin and Pramipexole in an Animal Model of Parkinson's Disease.

Abstract

Reports indicate that striatal dopaminergic damage induced by 6-hydoxydopamine (6-OHDA) can be blocked by C-terminal domain of tetanus toxin (Hc-TeTx), suggesting possible therapeutic potential of Hc-TeTx in Parkinson's disease (PD). Pramipexole (PPX), a D2/D3 dopaminergic agonist, is currently used in PD treatment. The purpose of this study was to gain some understanding of the actions of each drug, including potential antioxidant and anti-inflammatory effects and importantly, to determine whether the combination of the two drugs would be superior to each alone. Adult male Wistar rats were administered 6-OHDA into the dorso-lateral striatum, and the effects of Hc-TeTx fragment (20 μg/kg i.m. every 24 h) for 3 days; PPX (1 mg/kg p.o., every 12 h) for 30 days and their combination on various motor and neurochemical parameters were evaluated. Behavioral tests were carried out at 15 and 30 days post-treatments. At day 31, the animals were sacrificed and the levels of tyrosine hydroxylase (TH), reflecting dopaminergic activity in both striatum and substantia nigra, were evaluated. In addition, indices of astrogliosis, microgliosis, as well as oxidative stress in the striatum were determined. Both Hc-TeTx and PPX ameliorated the motor and neurochemical deficits induced by 6-OHDA lesion; however, the combination of the two drugs was not superior to each alone. Hence, at concentrations used in this study, no significant advantage in combining Hc-TeTx with PPX was noted. Although the results suggest similar neurochemical effects of the two compounds, further evaluation of different concentrations of Hc-TeTx and PPX as potential intervention in PD is warranted.

• Authors: Felipe Patricio, Irving Parra, Isabel Martínez, Francisca Pérez-Severiano, Sergio Montes, José Aguilera, Ilhuicamina Daniel Limón, Yousef Tizabi, Liliana Mendieta
• Journal: Neurotoxicity research (Neurotox Res) Vol. 35 Issue 3 Pg. 699-710 (Apr 2019) ISSN: 1476-3524 [Electronic] United States
• PMID: 30607904 (Publication Type: Journal Article)

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Antioxidants
• Antiparkinson Agents
• Peptide Fragments
• Tetanus Toxin
• tetanus toxin fragment C
• Pramipexole
• Oxidopamine

Topics

• Animals
• Anti-Inflammatory Agents, Non-Steroidal (pharmacology)
• Antioxidants (pharmacology)
• Antiparkinson Agents (pharmacology)
• Astrocytes (drug effects, metabolism, pathology)
• Corpus Striatum (drug effects, metabolism, pathology)
• Drug Therapy, Combination
• Gliosis (drug therapy, metabolism, pathology)
• Male
• Microglia (drug effects, metabolism, pathology)
• Motor Activity (drug effects)
• Oxidative Stress (drug effects, physiology)
• Oxidopamine
• Parkinsonian Disorders (drug therapy, metabolism, pathology)
• Peptide Fragments (pharmacology)
• Pramipexole (pharmacology)
• Random Allocation
• Rats, Wistar
• Tetanus Toxin (pharmacology)
• Time Factors