Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030567 (Parkinson's disease)
 63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purpose of this study was to investigate the potential neuroprotective effects of myricetin (flavonoid) and fraxetin (coumarin) on rotenone-induced apoptosis in SH-SY5Y cells, and the possible signal pathway involved in a neuronal cell model of Parkinson's disease. These two compounds were compared to N-acetylcysteine. The viability of cells was assessed by 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), and cytotoxicity was assayed by lactate dehydrogenase (LDH) released into the culture medium. Parameters related to apoptosis, such as caspase-3 activity, the cleavage of poly(ADP-ribose) polymerase and the levels of reactive oxygen species were also determined. Rotenone caused a time- and dose-dependent decrease in cell viability and the degree of LDH release was proportionally to the effects on cell viability. Cells were pretreated with fraxetin, myricetin and N-acetylcysteine at different concentrations for 30 min before exposure to rotenone. Cytotoxicity of rotenone (5 microM) for 16 h was significantly diminished as well as the release of LDH into the medium, by the effect of fraxetin, myricetin and N-acetylcysteine, with fraxetin (100 microM) and N-acetylcysteine (100 microM) being more effective than myricetin (50 microM). Rotenone-induced apoptosis in SH-SY5Y cells was detected by an increase in caspase-3 activity and in the cleavage of poly(ADP-ribose) polymerase. After exposing these cells to rotenone, a significant increase in reactive oxygen species preceded apoptotic events. Fraxetin (100 microM) and N-acetylcysteine (100 microM) not only reduced rotenone-induced reactive oxygen species formation, but also attenuated caspase-3 activity and poly(ADP-ribose) polymerase cleavage at 16 h against rotenone-induced apoptosis. The effect of fraxetin in both experiments was similar to that of N-acetylcysteine. These results demonstrated the protective action of fraxetin and suggest that it can reduce apoptosis, possibly by decreasing free radical generation in SH-SY5Y cells. Myricetin at 100 microM was without any preventive effect.
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PMID:Effect of fraxetin and myricetin on rotenone-induced cytotoxicity in SH-SY5Y cells: comparison with N-acetylcysteine. 1286 Apr 76

Rotenone-induced apoptosis is considered to contribute to the etiology of Parkinson's disease (PD). We try to prevent the apoptosis induced by rotenone toxicity with 50 microM myricetin, 100 microM fraxetin and 100 microM N-acetylcysteine (NAC) that protect against reactive oxygen species (ROS), on SH-SY5Y human neuroblastoma cell line. Morphological changes induced by rotenone and intracellular ROS were assessed in live SH-SY5Y dopaminergic cells by confocal microscopy using the fluorescent dyes, dihydroethidium and 2',7'-dichlorofluorescein diacetate (DCFH-DA). DNA fragmentation was assayed as index of apoptosis. We also investigated oxidative stress parameters such as the glutathione redox status and lipid peroxidation. The exposure of the SH-SY5Y cells to rotenone 5 microM for 16 h produced severe morphological changes, DNA fragmentation and significative increases in the levels of hydrogen peroxide and superoxide anion. These increases were reduced by a 30-min pretreatment with fraxetin 100 microM or NAC 100 microM. DNA laddering produced by rotenone treatment was also inhibited by fraxetin and NAC. Treatment with 5 microM rotenone induced loss of reduced glutathione (GSH) and increased cellular levels of oxidized glutathione (GSSG). Fraxetin and NAC treatments restored glutathione redox ratio diminished after rotenone challenge and decreased the levels of lipid peroxidation. These results suggest that the natural antioxidants, such as fraxetin, may prevent the apoptotic death of dopaminergic cells induced by rotenone and mediated by oxidative stress.
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PMID:Neuroprotective effect of fraxetin and myricetin against rotenone-induced apoptosis in neuroblastoma cells. 1512 May 78