tretinoin and Parkinson-Disease--Secondary

Parkinson's disease (PD) is a late-onset, progressive and neurodegenerative disorder of unknown etiology. Besides the other therapeutic approaches, new drug options in pharmacotherapy of PD are important. The aim of the present study was to investigate the effects of pioglitazone and retinoic acid, antioxidant and neuroprotective agents, on rotenone-induced model of PD in rats. Adult male Wistar rats (260-373 g) were subjects. Rotenone (2.5mg/kg, sc) was injected to rats for 70 days. At the end of rotenone administration, rats were treated with pioglitazone (10mg/kg, ip) and retinoic acid (1mg/kg, ip) or vehicles for 15 days. Then, rats were tested for evaluation of Parkinson signs by measurement of locomotor activity. In addition, dopamine levels were detected in striatum, hippocampus and hypothalamus in individual groups of control, rotenone and pioglitazone or retinoic acid-treated rats. Rotenone significantly reduced locomotor activity of the rats. It also significantly reduced dopamine levels in striatum and hippocampus, but not hypothalamus. Pioglitazone and retinoic acid reversed in reduction of locomotor activity significantly. Pioglitazone, but not retinoic acid, significantly reversed the reduced striatal dopamine level. Both drugs were ineffective on reduced levels of dopamine in hippocampus. Our results suggest that pioglitazone and retinoic acid have some beneficial effects on rotenone-induced model of PD in rats. Pioglitazone seems to be more effective than retinoic acid. These agents may be helpful for preventing or controlling of some signs of PD.

Topics: Animals; Antineoplastic Agents; Antioxidants; Disease Models, Animal; Hypoglycemic Agents; Male; Motor Activity; Neuroprotective Agents; Parkinson Disease, Secondary; Pioglitazone; Rats; Rats, Wistar; Rotenone; Thiazolidinediones; Tretinoin

Considerable evidence implicates the involvement of mitochondrial dysfunction in neurodegenerative diseases. 6OHDA is a mitochondrial complex I inhibitor which is frequently used to model Parkinson's disease-like cell loss. We investigated the cell death pathways triggered by 6OHDA in PC12 and P19 cells with a view to shedding light on the molecular basis of Parkinson's disease. We found that 6OHDA triggered mostly necrosis and less than 5% apoptosis in PC12 cells, whereas 6OHDA-induced death in P19 cells was apoptotic. While desipramine, a dopamine uptake blocker, attenuated 6OHDA-induced apoptosis in PC12 cells, this compound had no effect on the large scale necrotic death. Furthermore, desipramine failed to reduce apoptosis in 6OHDA-treated P19 cells, suggesting that the mechanism of 6OHDA toxicity does not require uptake via the dopamine transporter. As cell death triggered by 6OHDA was not blocked by free radical scavengers or NMDA receptor antagonists, a non-specific extracellular mechanism may be involved.

Topics: Animals; Antineoplastic Agents; Apoptosis; Aurintricarboxylic Acid; Biological Transport; Bisbenzimidazole; Carrier Proteins; Cell Membrane; Desipramine; Dopamine; Dopamine Plasma Membrane Transport Proteins; Dose-Response Relationship, Drug; Enzyme Inhibitors; Fluorescent Dyes; Free Radical Scavengers; In Situ Nick-End Labeling; Melatonin; Membrane Glycoproteins; Membrane Transport Proteins; Necrosis; Nerve Tissue Proteins; Neurons; NG-Nitroarginine Methyl Ester; Oxidopamine; Parkinson Disease, Secondary; PC12 Cells; Rats; Sympatholytics; Tretinoin; Tritium