Quebrachitol (2- O-methyl- l-inositol) attenuates 6-hydroxydopamine-induced cytotoxicity in rat fetal mesencephalic cell cultures

Naturally occurring plant substances have the potential to prevent oxidative damage in various pathophysiological conditions including neurodegenerative disorders. Recent findings indicate that impaired energy metabolism plays a prominent role in neurodegeneration. The present study investigated whe...

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Published in:	Food and chemical toxicology Vol. 44; no. 9; pp. 1544 - 1551
Main Authors:	Nobre Júnior, H.V., Cunha, G.M.A., Moraes, M.O., Luciana, M.F.D., Oliveira, R.A., Maia, F.D., Nogueira, M.A.S., Lemos, T.L.G., Rao, V.S.
Format:	Journal Article
Language:	English
Published:	Oxford Elsevier Ltd 01-09-2006 New York, NY Elsevier Science
Subjects:	2- O-Methyl- l-inositol 6-Hydroxydopamine Animals anti-inflammatory activity antioxidant activity antioxidants Antioxidants - pharmacology apoptosis Biological and medical sciences Cell Death - drug effects cell lines Cell Survival - drug effects Cells, Cultured cytoprotection Cytoprotection - drug effects Cytotoxicity dopamine Dose-Response Relationship, Drug Drug Combinations Fetal rat fetus Fetus - cytology free radical scavengers Inositol - analogs & derivatives Inositol - pharmacology Medical sciences Mesencephalic cell cultures Mesencephalon - drug effects Mesencephalon - embryology Mesencephalon - metabolism myo-inositol necrosis neurons Oxidative Stress - drug effects Oxidopamine - toxicity Phytotherapy plant-based foods Quebrachitol Rats Rats, Wistar structure-activity relationships Sympatholytics - toxicity Toxicology Tyrosine 3-Monooxygenase - metabolism Quebrachitol Cytotoxicity 2- O-Methyl- l-inositol Mesencephalic cell cultures Fetal rat 6-Hydroxydopamine Cell culture Inositol Rat Hepatoprotector Rodentia B-Vitamins In vitro 2-O-Methyl-L-inositol Vertebrata Mammalia Fetal cell Animal
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Summary:	Naturally occurring plant substances have the potential to prevent oxidative damage in various pathophysiological conditions including neurodegenerative disorders. Recent findings indicate that impaired energy metabolism plays a prominent role in neurodegeneration. The present study investigated whether quebrachitol (2- O-methyl- l-inositol) (QCT), a sugar like natural compound that was suggested to have both antioxidant and membrane stabilization activity prevents the cytotoxic effect of 6-hydroxydopamine (6-OHDA, 200 μM) on cultured rat fetal mesencephalic cells. While QCT (0.1–100 μg/ml) produced no effect per se on cell viability as measured in the 3[4,5-dimethylthiazole-2il]-2,5-diphenyltetrazolium bromide (MTT) test, it offered concentration-related protection against cell death induced by 6-OHDA. In addition, QCT demonstrated an antioxidant activity against 6-OHDA-induced oxidative stress as evidenced by reduced formation of nitrite–nitrate and thiobarbituric acid-related substances. Fluorescence microscopy using acridine orange/ethidium bromide double staining further affirmed the absence of 6-OHDA (200 μM)-induced morphological changes characteristic of apoptosis/necrosis in cultures pretreated with QCT (100 μg/ml). Also, results of tyrosine hydroxylase immunoreactivity indicated that 6-OHDA induces cell death in mesencephalic cultures affecting both TH + positive and TH − negative (TH + and TH −, respectively) and QCT pretreatment protects them from cell death, in a non-specific manner. Our data indicate that QCT has a cytoprotective role due, at least in part, to an antioxidant and free radical scavenging mechanism. Furthermore, the study suggests that inositol compounds might serve as leads in developing drugs for the treatment of various neurodegenerative disorders.
Bibliography:	http://dx.doi.org/10.1016/j.fct.2006.04.002 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0278-6915 1873-6351
DOI:	10.1016/j.fct.2006.04.002