Pharmacological investigations on potential of peroxisome proliferator-activated receptor-gamma agonists in hyperhomocysteinemia-induced vascular dementia in rats.
Summary of "Pharmacological investigations on potential of peroxisome proliferator-activated receptor-gamma agonists in hyperhomocysteinemia-induced vascular dementia in rats."
The present study has been designed to investigate the potential of peroxisome proliferator-activated receptor-gamma ([PPAR]-γ) agonists, pioglitazone, and rosiglitazone in hyperhomocysteinemia-induced vascular dementia of rats. l-methionine was administered for 8 weeks to induce hyperhomocysteinemia and associated vascular dementia. Pioglitazone and rosiglitazone were administered to l-methionine-treated rats for 4 weeks (starting from 5th to 8th weeks of methionine treatment). Donepezil served as a positive control in this study. On 52nd day onward, the animals were exposed to Morris water maze (MWM) for testing learning and memory abilities. Vascular endothelial function, serum nitrite/nitrate levels, brain thiobarbituric acid reactive species (TBARS), brain reduced glutathione (GSH) levels, and brain acetylcholinesterase (AChE) activity were also measured. l-methionine-treated animals have shown impairment of learning, memory, endothelial function, decrease in serum nitrite/nitrate levels, and brain GSH levels along with increase in brain TBARS levels and AChE activity. Pioglitazone, rosiglitazone, and donepezil significantly improved hyperhomocysteinemia-induced impairment of learning, memory, endothelial dysfunction, and changes in various biochemical parameters. It is concluded that pioglitazone and rosiglitazone may be considered as potential pharmacological agents for the management of hyperhomocysteinemia-induced vascular dementia.
Affiliation
Pharmacology Division, Department of Pharmaceutical Sciences and Drug Research, Faculty of Medicine, Punjabi University, Patiala-147002, Punjab, India.
Journal Details
This article was published in the following journal.
Name: Neuroscience
ISSN: 1873-7544
Pages: 322-33
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/21777659
- DOI: http://dx.doi.org/10.1016/j.neuroscience.2011.07.002
Medical and Biotech [MESH] Definitions
Peroxisome Proliferator-activated Receptors
TRANSCRIPTION FACTORS that are activated by ligands and heterodimerize with RETINOID X RECEPTORS and bind to peroxisome proliferator response elements in the promoter regions of target genes.
Thiazolidinediones
THIAZOLES with two keto oxygens. Members are insulin-sensitizing agents which overcome INSULIN RESISTANCE by activation of the peroxisome proliferator activated receptor gamma (PPAR-gamma).
Mediator Complex Subunit 1
A mediator complex subunit that is believed to play a key role in the coactivation of nuclear receptor-activated transcription by the mediator complex. It interacts with a variety of nuclear receptors including RETINOIC ACID RECEPTORS; THYROID HORMONE RECEPTORS; VITAMIN D RECEPTORS; PEROXISOME PROLIFERATOR-ACTIVATED RECEPTORS; ESTROGEN RECEPTORS; and GLUCOCORTICOID RECEPTORS.
Nafenopin
A peroxisome proliferator that is used experimentally to promote liver tumors. It has been used as an antihyperlipoproteinemic agent.
Receptor, Par-2
A G-protein-coupled, proteinase-activated receptor that is expressed in a variety of tissues including ENDOTHELIUM; LEUKOCYTES; and the GASTROINTESTINAL TRACT. The receptor is activated by TRYPSIN, which cleaves off the N-terminal peptide from the receptor. The new N-terminal peptide is a cryptic ligand for the receptor. The uncleaved receptor can also be activated by the N-terminal peptide present on the activated THROMBIN RECEPTOR and by small synthetic peptides that contain the unmasked N-terminal sequence.
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