1.Research of bornrol promote drugs through blood-brain barrier.
Xuxiao LV ; Mingjiang SUN ; Fengzhi SUN
China Journal of Chinese Materia Medica 2012;37(7):878-881
Malignant tumor, epilepsy, dementia, cerebral ischemia and other brain diseases have very high rates of disability and mortality. Currently, many drugs are developed to treat such diseases and the effect is obviously. But they can not achieve the purpose to control these diseases because many of the drugs can not pass through the blood-brain barrier (BBB). Therefore, the treatment is not good. Borneol as the represent of the aromatic resuscitation medicine, it has strong fat-soluble active ingredients, small molecular weight, volatile and through the BBB quickly. It can also promote other therapeutic drugs through the BBB. It has two-ways regulations on BBB permeability and the damage of brain tissue is small, this have important theoretical significances and application values.
Animals
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Biological Transport
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drug effects
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Blood-Brain Barrier
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drug effects
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metabolism
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Bornanes
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pharmacology
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Brain
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drug effects
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metabolism
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Humans
2.Effects of extremely low frequency electromagnetic field and its combination with lead on the antioxidant system in mouse.
Yun LIU ; Enqi WENG ; Ying ZHANG ; Rong HONG
Chinese Journal of Industrial Hygiene and Occupational Diseases 2002;20(4):263-265
OBJECTIVETo study the effects of extremely low frequency electromagnetic field(ELF EMF) and its combination with lead on the antioxidant system in mouse brain and liver tissues.
METHODMice were exposed to a 50 Hz sinusoidal 0.2 mT or 6.0 mT EMF for 2 weeks. At the same time, some groups were exposed to lead(50 mg/kg). After the exposure, the antioxidant system and cell membrane fluidity in brain and liver were measured.
RESULTSMalondiadehyde(MDA) content in brain and liver increased from the control levels of (1.33 +/- 0.12) and (3.95 +/- 0.21) nmol/mg pro to (1.35 +/- 0.09) and (6.15 +/- 0.28) nmol/mg pro respectively following 0.2 mT exposure, and to (3.98 +/- 0.10) and (6.50 +/- 0.79) nmol/mg pro respectively following 6.0 mT exposure. Total antioxidant capability(T-AOC) in brain and liver decreased from the control levels of (4.39 +/- 0.48) and (2.45 +/- 0.21) U/mg pro to (3.99 +/- 0.39) and (1.92 +/- 0.32) U/mg pro respectively following 0.2 mT, and to (3.12 +/- 0.37) and (1.57 +/- 0.14) U/mg pro respectively following 6.0 mT. GSH content decreased only in liver tissue from the control level of (194.60 +/- 20.93) mg/g pro to (189.24 +/- 5.61) mg/g pro(0.2 mT) and (153.04 +/- 1.18) mg/g pro(6.0 mT). Cellular membrane fluidity decreased from the control levels of (1.396 +/- 0.040) and (2.899 +/- 0.552) to (1.224 +/- 0.190) and (1.894 +/- 0.0761) (0.2 mT), (1.159 +/- 0.179) and (1.516 +/- 0.204)(6.0 mT) respectively. Compared with single EMF exposure(6.0 mT), EMF combined with lead exposure induced remarkable increase in MDA, GSH content and T-AOC and decrease in cell membrane fluidity both in the brain and liver, and increase in SOD activity only in liver.
CONCLUSIONELF EMF might alter the metabolism of free radicals, decrease anti-oxidant capability and enhance lipid peroxidation. The combination of EMF with lead showed synergic effects on lipid peroxidation.
Animals ; Antioxidants ; metabolism ; Brain ; drug effects ; metabolism ; radiation effects ; Electromagnetic Fields ; adverse effects ; Glutathione ; analysis ; Lead ; toxicity ; Lipid Peroxidation ; drug effects ; radiation effects ; Liver ; drug effects ; metabolism ; radiation effects ; Membrane Fluidity ; drug effects ; radiation effects ; Mice ; Superoxide Dismutase ; metabolism
3.Progress in regulation effect of aromatic refreshing traditional Chinese medicine on BBB permeability and its mechanism.
Li-Ping WANG ; Jian-Fang FENG ; Kai-Li HU
China Journal of Chinese Materia Medica 2014;39(6):949-954
The blood-brain barrier (BBB) protects the brain against unwanted substances, while, at the same time, limits the transport of many drugs into the brain. Aromatic refreshing traditional Chinese medicine (TCM) can induce resuscitation and modify the permeability of BBB, promoting other drugs entering into the brain with brain protection effect. This paper mainly reviews the research progress in regulation effects and mechanism of usual aromatic refreshing TCM, such as borneol, moschus, styrax, benzoinum and Tatarinow Sweetflag Rhizome, on BBB permeability. To broaden the application of these drugs in modern pharmaceutics in the future, the relatively research should emphasis on combining aromatic refreshing TCM with new formulations and technologies in pharmaceutics, providing novel promising strategies for brain diseases therapy.
Animals
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Blood-Brain Barrier
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drug effects
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metabolism
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Humans
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Medicine, Chinese Traditional
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methods
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Permeability
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drug effects
4.Effects of daidzein on the Ca2+i of synapse in different brain regions of the aged mice.
Chinese Journal of Applied Physiology 2005;21(1):103-104
Aging
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Animals
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Brain
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drug effects
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metabolism
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Calcium
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metabolism
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Female
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Isoflavones
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pharmacology
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Male
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Mice
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Mice, Inbred Strains
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Synapses
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drug effects
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metabolism
5.Effect of Gastrodin on Early Brain Injury and Neurological Outcome After Subarachnoid Hemorrhage in Rats.
Xinzhi WANG ; Shuyue LI ; Jinbang MA ; Chuangang WANG ; Anzhong CHEN ; Zhenxue XIN ; Jianjun ZHANG
Neuroscience Bulletin 2019;35(3):461-470
Gastrodin is a phenolic glycoside that has been demonstrated to provide neuroprotection in preclinical models of central nervous system disease, but its effect in subarachnoid hemorrhage (SAH) remains unclear. In this study, we showed that intraperitoneal administration of gastrodin (100 mg/kg per day) significantly attenuated the SAH-induced neurological deficit, brain edema, and increased blood-brain barrier permeability in rats. Meanwhile, gastrodin treatment significantly reduced the SAH-induced elevation of glutamate concentration in the cerebrospinal fluid and the intracellular Ca overload. Moreover, gastrodin suppressed the SAH-induced microglial activation, astrocyte activation, and neuronal apoptosis. Mechanistically, gastrodin significantly reduced the oxidative stress and inflammatory response, up-regulated the expression of nuclear factor erythroid 2-related factor 2, heme oxygenase-1, phospho-Akt and B-cell lymphoma 2, and down-regulated the expression of BCL2-associated X protein and cleaved caspase-3. Our results suggested that the administration of gastrodin provides neuroprotection against early brain injury after experimental SAH.
Animals
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Apoptosis
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drug effects
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Astrocytes
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drug effects
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metabolism
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Benzyl Alcohols
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administration & dosage
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Blood-Brain Barrier
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drug effects
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metabolism
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Brain
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drug effects
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metabolism
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Brain Edema
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etiology
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prevention & control
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Calcium
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metabolism
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Glucosides
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administration & dosage
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Glutamic Acid
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metabolism
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Male
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Microglia
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drug effects
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metabolism
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Neurons
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drug effects
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Neuroprotective Agents
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administration & dosage
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Oxidative Stress
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drug effects
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Rats, Sprague-Dawley
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Subarachnoid Hemorrhage
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complications
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metabolism
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prevention & control
6.Enhanced expression of aquaporin-9 in rat brain edema induced by bacterial lipopolysaccharides.
Huaili, WANG ; Runming, JIN ; Peichao, TIAN ; Zhihong, ZHUO
Journal of Huazhong University of Science and Technology (Medical Sciences) 2009;29(2):150-5
To investigate the role of AQP9 in brain edema, the expression of AQP9 in an infectious rat brain edema model induced by the injection of lipopolysaccharide (LPS) was examined. Immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR) analysis demonstrated that the expressions of AQP9 mRNA and protein at all observed intervals were significantly increased in LPS-treated animals in comparison with the control animals. Time-course analysis showed that the first signs of blood-brain barrier disruption and the increase of brain water content in LPS-treated animals were evident 6 h after LPS injection, with maximum value appearing at 12 h, which coincided with the expression profiles of AQP9 mRNA and protein in LPS-treated animals. The further correlation analysis revealed strong positive correlations among the brain water content, the disruption of the blood-brain barrier and the enhanced expressions of AQP9 mRNA and protein in LPS-treated animals. These results suggested that the regulation of AQP9 expression may play important roles in water movement and in brain metabolic homeostasis associated with the pathophysiology of brain edema induced by LPS injection.
Aquaporins/genetics
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Aquaporins/*metabolism
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Blood-Brain Barrier/metabolism
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Brain/drug effects
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Brain/physiology
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Brain Edema/chemically induced
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Brain Edema/*metabolism
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Lipopolysaccharides
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Rats, Sprague-Dawley
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Water/physiology
7.Effects of postnatal lambda-cyhalothrin exposure on synaptic proteins in ICR mouse brain.
Xun-Di BAO ; Qu-Nan WANG ; Fang-Fang LI ; Xiao-Yu CHAI ; Ye GAO
Chinese Journal of Industrial Hygiene and Occupational Diseases 2011;29(4):284-288
OBJECTIVETo evaluate the influence on the synaptic protein expression in different brain regions of ICR mice after lambda-cyhalothrin (LCT) exposure during postnatal period.
METHODSTwo male and 4 female healthy ICR mice were put in one cage. It was set as pregnancy if vaginal plug was founded. Offspring were divided into 5 groups randomly, and exposed to LCT (0.01% DMSO solution) at the doses of 0.1, 1.0 and 10.0 mg/kg by intragastric rout every other day from postnatal days (PND) 5 to PND13, control animals were treated with normal saline or DMSO by the same route. The brains were removed from pups on PND 14, the synaptic protein expression levels in cortex, hippocampus and striatum were measured by western blot.
RESULTSGFAP levels of cortex and hippocampus in the LCT exposure group increased with doses, as compared with control group (P < 0.05), while Tuj protein expression did not change significantly in the various brain regions of ICR mice. GAP-43 protein expression levels in the LCT exposed mouse hippocampus and in female ICR mouse cortex increased with doses, as compared with control group (P < 0.05). Presynaptic protein (Synapsin I) expression levels did not change obviously in various brain regions. However, postsynaptic density protein 95 (PSD95) expression levels of the hippocampus and striatum in male offspring of 10.0 mg/kg LCT group, of cortex of female LCT groups, and of female offspring in all exposure groups, of striatum, in 1.0 or 10.0 mg/kg LCT exposure groups significantly decreased (P < 0.05).
CONCLUSIONSEarly postnatal exposure to LCT affects synaptic protein expression. These effects may ultimately affect the construction of synaptic connections.
Animals ; Animals, Newborn ; Brain ; drug effects ; metabolism ; Corpus Striatum ; drug effects ; metabolism ; Female ; Hippocampus ; drug effects ; metabolism ; Male ; Mice ; Mice, Inbred ICR ; Nitriles ; toxicity ; Pyrethrins ; toxicity ; Synapsins ; metabolism
8.Effects of Dengzhan Xixin on blood-brain barrier permeability and metabolites after cerebral ischemia-reperfusion injuries.
Hua LIU ; Weijing LIAO ; Li WEI ; Hao LEI
China Journal of Chinese Materia Medica 2009;34(2):208-211
OBJECTIVEThe investigated the effects of Dengzhan Xixin on brain water content, blood-brain barrier (BBB) permeability, T2-weighted imaging (T2WI), metabolites and the lesion ratio after cerebral ischemia-reperfusion injuries (IRI).
METHODThe 65 rats were randomly individed into three groups, the sham-operated group, the ischemia-reperfusion group and the Dengzhan Xixin treatment group. The models of ischemia-reperfusion of middle cerebral artery in rats were established by placing an intraluminal suture. The Dengzhan Xixin treatment group were injected 10% Dengzhan Xixin injection 22.5 mg kg(-1) after ischemia 1.5 h. The sh am-operated group (n=5) were sacrificed on 1 to measure brain water content and BBB permeability. The rats of the ischemia-reperfusion group (n=30) and the Dengzhan Xixin treatment group (n=30) were sacrificed at reperfusion for 6 h, 12 h, 1 d, 2 d, 4 d, 7 d, respectively, after ischemia 1.5 h. The additional 35 rats were individed into the same three groups. The changes of T2WI and metabolites in the brain were observed, and rats were sacrificed at reperfusion for 1 d, 2 d, 4 d after ischemia 1.5 h to determine the lesion ratio by TTC.
RESULTIn the ischemia-reperfusion group, brain water content(77.93+/-0.68)% and BBB permeability (3.77+/-0.28) increased after reperfusion for 6 h. The peak time of brain water content was at 4 d (83.82+/-0.49)% and BBB permeability was at 2 d (5.51+/-0.24)%. In the ischemia-reperfusion group and the Dengzhan Xixin treatment group, there were hyperintense signals in the injury region of T2WI. In the ischemia-reperfusion group after reperfusion for 1 d, the ratio of NAA/Cr decreased and Cho/Cr increased. In the Dengzhan Xixin treatment group, the ratio of NAA/Cr increased and Cho/Cr decreased. In the treatment group, the lesion ratio decreased by TTC was 16.78+/-1.45 and in the ischemia-reperfusion group was 21.27+/-1.73 at 2 d.
CONCLUSIONDengzhan Xixin may relieve cerebral ischemia-reperfusion injury by influencing the metabolites of brain, stabilizing BBB and decreasing brain edema.
Animals ; Blood-Brain Barrier ; drug effects ; metabolism ; Brain Ischemia ; complications ; metabolism ; pathology ; Flavonoids ; pharmacology ; Male ; Permeability ; drug effects ; Rats ; Rats, Wistar ; Reperfusion Injury ; complications ; metabolism ; pathology ; Water ; metabolism
9.Effect of FGF-21 on learning and memory ability and antioxidant capacity in brain tissue of D-galactose-induced aging mice.
Yin-Hang YU ; Gui-Ping REN ; Yao-Nan LIU ; Su-Su QU ; Fu-Liang BAI ; Tong ZHANG ; Wen-Fei WANG ; Gui-You TIAN ; Xian-Long YE ; De-Shan LI
Acta Pharmaceutica Sinica 2014;49(7):1000-1006
This study aims to investigate the effects of fibroblast growth factor 21 (FGF-21) on learning and memory abilities and antioxidant capacity of D-galactose-induced aging mice. Kunming mice (37.1 +/- 0.62) g were randomly divided into normal control group, model group and FGF-21 high, medium and low dose groups (n = 8). Each group was injected in cervical part subcutaneously with D-galactose 180 mg x kg(-1) x d(-1) once a day for 8 weeks. At the same time, FGF-21-treated mice were administered with FGF-21 by giving subcutaneous injection in cervical part at the daily doses of 5, 2 and 1 mg x kg(-1) x d(-1). The normal control group was given with normal saline by subcutaneous injection in cervical part. At seventh week of the experiment, the learning and memory abilities of mice were determined by water maze and jumping stand tests. At the end of the experiment, the mice were sacrificed and the cells damage of hippocampus was observed by HE staining in each group. Reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT) and total antioxidant capacity (T-AOC) in the brain of mice were determined. The results showed that different doses of FGF-21 could reduce the time reaching the end (P < 0.01 or P < 0.05) and the number of touching blind side (P < 0.01 or P < 0.05) in the water maze comparing with the model group. It could also prolong the latency time (P < 0.05) and decrease the number of errors (P < 0.01 or P < 0.05) in the step down test. The result of HE staining showed that FGF-21 could significantly reduce brain cell damage in the hippocampus. The ROS and MDA levels of three different doses FGF-21 treatment group reduced significantly than that of the model group [(5.58 +/- 1.07), (7.78 +/- 1.92), (9.03 +/- 1.77) vs (12.75 +/- 2.02) pmol (DCF) x min(-1) x mg(-1), P < 0.01 or P < 0.05], [(2.92 +/- 0.71), (4.21 +/- 0.81), (4.41 +/- 0.97) vs (5.62 +/- 0.63) nmol x mg(-1) (protein), P < 0.01]. Comparing with the model group, the activities of SOD, GPx, CAT and T-AOC of the three different doses FGF-21 treatment groups were also improved in a dose-dependent manner. This study demonstrates that FGF-21 can ameliorate learning and memory abilities of D-galactose induced aging mice, improve the antioxidant abilities in brain tissue and delay brain aging. This finding provides a theoretical support for clinical application of FGF-21 as a novel therapeutics for preventing aging.
Aging
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drug effects
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Animals
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Antioxidants
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metabolism
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Brain
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drug effects
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Catalase
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metabolism
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Fibroblast Growth Factors
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pharmacology
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Galactose
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Glutathione Peroxidase
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metabolism
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Hippocampus
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drug effects
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Malondialdehyde
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metabolism
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Maze Learning
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drug effects
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Memory
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drug effects
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Mice
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Superoxide Dismutase
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metabolism
10.Effect of acrylamide on creatine kinase and adenosine triphosphate in brain of mice and its significance.
Qiuyue HE ; Manfu HAN ; Mingli RAO
Chinese Journal of Industrial Hygiene and Occupational Diseases 2002;20(3):195-196
OBJECTIVETo explore the changes of brain energy metabolism following acrylamide (ACR) poisoning.
METHODSCreatie kinase (CK), adenosine triphosphate (ATP), adenosine diphosphate(ADP), adenosine 5'-monophosphate(AMP) and glucose contents in brain were observed in O1a mice and 6J mice following ACR intoxication by enzyme analytical method.
RESULTSATP, CK and glucose levels decreased transiently in O1a mice, while ATP level in 6J mice was significantly decreased (1.76 mumol/g, P < 0.01), as compared to the control (2.53 mumol/g) but ADP and AMP were increased, glucose was decreased. The activity of CK in poisoned group (1.13 mumol/g, P < 0.01) was lower than that of control (3.16 mumol/g and lasted for 5 weeks).
CONCLUSIONThe influence of ACR on O1a mice was slight and reversible but on 6J mice was severe and lasting. There was severe damage to the potential energy supply compensation, which might be the biochemical basis of neuron damage induced by acrylamide.
Acrylamide ; poisoning ; Adenosine Triphosphate ; analysis ; Animals ; Brain ; drug effects ; metabolism ; Creatine Kinase ; analysis ; Energy Metabolism ; drug effects ; Glucose ; analysis ; Mice