Safiulina 2006 Toxicol Sci: Difference between revisions
No edit summary |
No edit summary ย |
||
(5 intermediate revisions by 4 users not shown) | |||
Line 1: | Line 1: | ||
{{Publication | {{Publication | ||
|title=Safiulina D, Peet N, Seppet E, Zharkovsky A, Kaasik A (2006) Dehydroepiandrosterone inhibits | |title=Safiulina D, Peet N, Seppet E, Zharkovsky A, Kaasik A (2006) Dehydroepiandrosterone inhibits Complex I of the mitochondrial respiratory chain and is neurotoxic ''in vitro'' and ''in vivo'' at high concentrations. Toxicol Sci 93:348-56. | ||
|info=[http://www.ncbi.nlm.nih.gov/pubmed/16849397 PMID: 16849397] | |info=[http://www.ncbi.nlm.nih.gov/pubmed/16849397 PMID: 16849397 Open Access] | ||
|authors=Safiulina D, Peet N, Seppet E, Zharkovsky A, Kaasik A | |authors=Safiulina D, Peet N, Seppet E, Zharkovsky A, Kaasik A | ||
|year=2006 | |year=2006 | ||
|journal=Toxicol Sci | |journal=Toxicol Sci | ||
|abstract=Dehydroepiandrosterone (DHEA) is widely used as a food supplement and considered to be relatively safe. In animal studies, however, additions of high concentrations of DHEA to the diet have led to hepatotoxicity as well as liver mitochondrial dysfunction. This study was therefore designed to find out whether DHEA is able to inhibit the respiratory activity also in neuronal mitochondria and to reveal whether this leads to functional disturbance in the brain. Using different mitochondrial substrates, we show here that DHEA suppresses the mitochondrial respiration in permeabilized neurons (half maximal inhibitory concentration 13ฮผM) by inhibiting | |abstract=Dehydroepiandrosterone (DHEA) is widely used as a food supplement and considered to be relatively safe. In animal studies, however, additions of high concentrations of DHEA to the diet have led to hepatotoxicity as well as liver mitochondrial dysfunction. This study was therefore designed to find out whether DHEA is able to inhibit the respiratory activity also in neuronal mitochondria and to reveal whether this leads to functional disturbance in the brain. Using different mitochondrial substrates, we show here that DHEA suppresses the mitochondrial respiration in permeabilized neurons (half maximal inhibitory concentration 13ฮผM) by inhibiting Complex I of the mitochondrial electron transport chain. Treatment with DHEA was associated with increased glucose expenditure in intact cultures and led to neuronal death. The latter was most prominent in hypoglycemic conditions. Mice fed with pellet containing 0.6% DHEA for 3 months showed a significant neuronal loss in the cerebral cortex and hippocampus, a slightly decreased dopamine/dihydroxyphenylacetic acid ratio, as well as motor impairment. The main conclusion of the present study is that high concentrations of DHEA inhibit complex I of the mitochondrial respiratory chain and are neurotoxic ''in vitro'' and ''in vivo''. | ||
|keywords=Mitochondria, Neurosteroids, Neurodegeneration, Neurotoxicity, Complex I of the mitochondrial electron transport chain, Dehydroepiandrosterone | |keywords=Mitochondria, Neurosteroids, Neurodegeneration, Neurotoxicity, Complex I of the mitochondrial electron transport chain, Dehydroepiandrosterone | ||
|mipnetlab= | |mipnetlab=EE Tartu Paju K | ||
|discipline=Mitochondrial Physiology, Biomedicine | |discipline=Mitochondrial Physiology, Biomedicine | ||
}} | }} | ||
{{Labeling | {{Labeling | ||
| | |area=Respiration, Pharmacology;toxicology | ||
|diseases=Neurodegenerative | |||
|organism=Rat | |organism=Rat | ||
|tissues=Nervous system | |tissues=Nervous system | ||
| | |preparations=Isolated mitochondria | ||
|enzymes=Complex I | |enzymes=Complex I | ||
| | |couplingstates=OXPHOS, ET | ||
|pathways=N | |||
|instruments=Oxygraph-2k | |||
|discipline=Mitochondrial Physiology, Biomedicine | |discipline=Mitochondrial Physiology, Biomedicine | ||
}} | }} |
Latest revision as of 15:54, 13 November 2017
Safiulina D, Peet N, Seppet E, Zharkovsky A, Kaasik A (2006) Dehydroepiandrosterone inhibits Complex I of the mitochondrial respiratory chain and is neurotoxic in vitro and in vivo at high concentrations. Toxicol Sci 93:348-56. |
Safiulina D, Peet N, Seppet E, Zharkovsky A, Kaasik A (2006) Toxicol Sci
Abstract: Dehydroepiandrosterone (DHEA) is widely used as a food supplement and considered to be relatively safe. In animal studies, however, additions of high concentrations of DHEA to the diet have led to hepatotoxicity as well as liver mitochondrial dysfunction. This study was therefore designed to find out whether DHEA is able to inhibit the respiratory activity also in neuronal mitochondria and to reveal whether this leads to functional disturbance in the brain. Using different mitochondrial substrates, we show here that DHEA suppresses the mitochondrial respiration in permeabilized neurons (half maximal inhibitory concentration 13ฮผM) by inhibiting Complex I of the mitochondrial electron transport chain. Treatment with DHEA was associated with increased glucose expenditure in intact cultures and led to neuronal death. The latter was most prominent in hypoglycemic conditions. Mice fed with pellet containing 0.6% DHEA for 3 months showed a significant neuronal loss in the cerebral cortex and hippocampus, a slightly decreased dopamine/dihydroxyphenylacetic acid ratio, as well as motor impairment. The main conclusion of the present study is that high concentrations of DHEA inhibit complex I of the mitochondrial respiratory chain and are neurotoxic in vitro and in vivo. โข Keywords: Mitochondria, Neurosteroids, Neurodegeneration, Neurotoxicity, Complex I of the mitochondrial electron transport chain, Dehydroepiandrosterone
โข O2k-Network Lab: EE Tartu Paju K
Labels: MiParea: Respiration, Pharmacology;toxicology
Pathology: Neurodegenerative
Organism: Rat Tissue;cell: Nervous system Preparation: Isolated mitochondria Enzyme: Complex I
Coupling state: OXPHOS, ET Pathway: N HRR: Oxygraph-2k