Munir Qazzaz | Birzeit University (original) (raw)
Books by Munir Qazzaz
Papers by Munir Qazzaz
Towards New Therapies for Parkinson's Disease, 2011
Biological Trace Element Research, 2013
Acta Biologica Hungarica, 1999
1. The application of the volatile anaesthetics, halothane and isoflurane (1% v/v and 2% v/v), to... more 1. The application of the volatile anaesthetics, halothane and isoflurane (1% v/v and 2% v/v), to the CNS of Lymnaea reduced the firing frequency of the small weakly coupled pedal A cluster (PeA) neurones, which eventually become quiescent. There was no change in their resting membrane potential. 2. Met-enkephalin significantly increased the coupling coefficient between PeA neurones. 3. The volatile anaesthetics decreased the coupling coefficient even in the presence of met-enkephalin. 4. These effects were dose dependent and the effects of halothane were more rapid than those of isoflurane, reflecting their different anaesthetic potencies.
There is a substantial emerging literature on the complexity and plasticity of the apparently sim... more There is a substantial emerging literature on the complexity and plasticity of the apparently simple electrical synapses [ES]. Here we draw attention to some of the most recent findings in this rapidly evolving field. • ES are ubiquitous, found in all multicellular animals and structurally underlain by gap junctions. Gap junctions are topographically similar in vertebrates and invertebrates, but based on different mutually exclusive connexins and innexins respectively. • It is now clear that ES may be modulated and exhibit plasticity in addition to promoting synergy between coupled neurons according to the strength of coupling. Strong electrical coupling promotes synchronous activity while weak coupling may desynchronise coupled neurons. • Chemical synapses may modulate ES conductances and may regulate the degree of coupling between neurons. Because ES act as low pass filters, prolonged spike after-hyperpolarisations can allow them to act as inhibitory connections, but modifications...
The actions of clinical concentrations of volatile anaesthetic halothane and isoflurane were comp... more The actions of clinical concentrations of volatile anaesthetic halothane and isoflurane were compared with those of pentobarbitone on identified neurons of the pond snail Lymnaea stagnalis. Application of halothane and isoflurane (1% v/v and 2% v/v), to the CNS of Lymnaea caused the strongly electrically coupled neurons VD1 and RPD2 to become quiescent, with a significant increase in membrane potential and a significant reduction in their coupling coefficient. These results clearly demonstrate that the volatile anaesthetics and barbiturates have different mechanisms of action at electrical synapses. The effects of volatile anaesthetics were dose dependent, and the actions of halothane were more rapid than those of isoflurane, reflecting their different anaesthetic potencies. Sodium-pentobarbitone had markedly different effects from the volatile anaesthetics. Clinical concentrations of pentobarbitone (100 ± M) caused VD1 and RPD2 to become quiescent with no significant change in eith...
Phthalate esters are industrial chemicals widely used in cosmetics, plastics bottles and medical ... more Phthalate esters are industrial chemicals widely used in cosmetics, plastics bottles and medical devices, and the risk of exposure to phthalates is on the increase. In recent years, many studies have been carried out on the possible health hazards of phthalates, including the effect on reproduction. In this study rats were injected twice weekly with Di-butyl Phthalates (DBP) or Di (2-Ethylhexyl) Phthalates (DEHP) (100 mg/kg) and cohabited with male rats for one month. Fertility and mortality rates as well as fecundity were impacted significantly. Fertility rate decreased from 87 % in control rsats to 67 % in DBP treated and 50 % in DEHP treated rats. Similarly mortality rate in new born litters increased from 2.8 % in control rats to 52.3 % in DBP treated and 31.3 % in DEHP treated rats. Fecundity rate which expresses the average number of litters in each delivery was reduced from 8.2 in control rats to 7.3 in DBP treated and 5.3 in DEHP treated rats. No significant changes were obs...
Frontiers in Physiology, May 31, 2019
Differential effects of volatile general anaesthetics and sodium pentobarbital on input resistanc... more Differential effects of volatile general anaesthetics and sodium pentobarbital on input resistance [R m ], membrane time constant [ m ] and capacitance [C m ] of VD1 and RPD2 neurons of Lymnaea are reported in this paper. The volatile anaesthetics halothane and isoflurane caused a significant reduction in the input resistance, membrane time constant and capacitance in a dose dependent manner and halothane was more potent than isoflurane. The clinical concentration [100 M] of pentobarbitone caused no change in R m , m and C m of VD1 and RPD2, whereas 2.0 and 0.5 mM pentobarbitone increased them significantly during phase I but caused no change in these parameters during phase II.
Biological Trace Element Research
In these experiments we have tested the effect of bis(acetato)tetrakis (imidazole) copper(II) on ... more In these experiments we have tested the effect of bis(acetato)tetrakis (imidazole) copper(II) on the release and uptake of 14C-GABA and 3H-glutamate from brain slices and brain cortical synaptosomes. Cu(OAc)2(Im)4 in concentrations ranging from 1 to 100 microM has increased the release of GABA and glutamate from brain slices and synaptosomal preparations in a dose-related manner when the effect on GABA release is two-fold greater than glutamate and 10-fold greater than alanine. Pretreatment with a GABA uptake inhibitor such as 1-2 mM nipecotic acid has no effect on 14C-GABA release, whereas hydroxy aspartate, the glutamate uptake inhibitor, has elevated the stimulated release of glutamate. Copper(II) chloride, the inorganic form of copper, had no significant effect either on GABA release or on glutamate release. The stimulated release of exogenous GABA and glutamate was Ca2+-dependent, because it was inhibited by EGTA, and neuronal, because it was blocked by tetrodotoxin. The recent...
Molecular Brain, 2016
Concerns have risen regarding the potential side effects of clinical exposure of the pediatric po... more Concerns have risen regarding the potential side effects of clinical exposure of the pediatric population to inhalational anesthetics, and how they might impact cognitive, learning, and memory functions. However, neither the mechanisms of anesthetic cytotoxicity, nor potential protective strategies, have yet been fully explored. In this study, we examined whether two of the most commonly used inhalational anesthetics, sevoflurane and desflurane, affect neuronal viability and synaptic network assembly between cultured rat cortical neurons. Primary rat cortical neuron cultures were exposed to equipotent sevoflurane or desflurane for 1 hour. Neuron viability, synaptic protein expression, mitochondrial morphology, and neurite growth were assayed with immunostaining and confocal microscopy techniques. The effects of anesthetics on the functional development of neural networks were evaluated with whole-cell patch clamp recordings of spontaneous synaptic currents. Our results demonstrate that an acute exposure to sevoflurane and desflurane inhibits the development of neurite processes, impacts the mitochondria, and compromises synaptic proteins - concomitant with a reduction in synaptic function in mature networks. Interestingly, pretreatment of neurons with a mitochondrial division inhibitor (Mdivi-1) not only protected mitochondria integrity but also played a protective role against anesthetic-induced structural and functional neurotoxicity. We show that Mdivi-1 likely plays a protective role against certain harmful effects of general anesthetics on primary rat neuronal cultures. In addition, Mdivi-1 alone plays a direct role in enhancing growth and modulating synaptic activity. This study highlights the importance of further study into possible protective agents against anesthetic neurotoxicity.
Journal of environmental biology / Academy of Environmental Biology, India, 2014
In the present work, the effect of exposure to cigarette smoke on male fertility in rats, as char... more In the present work, the effect of exposure to cigarette smoke on male fertility in rats, as characterized by changes in the relative weight of sex organs, epididymal sperm count, activity of marker enzymes and DNA damage was evaluated. Exposure of rats to cigarette smoke caused a gradual decrease in total body weight gain and relative weight of the epididymis and seminal vesicles by 30 and 40% respectively. Epididymal sperm count was reduced significantly by 25% (P 0.05) after 2 weeks and by 41% (P 0.001) after 4 weeks of exposure. Exposure to cigarette smoke had reduced the activity of sorbitol dehydogenase by 18% (P < or = 0.05) and increased the activity of lactate dehydrogenase by 28% (P < or = 0.05). The changes in both key enzymes were significant, which reflected the inhibitory effect of cigarette smoke on spermatogenesis and sperm maturation. The toxic effect of exposure could be explained partially due to induction of DNA damage and oxidative stress as shown by the s...
Background Silver nanoparticles (AgNPs), owing to their effective antimicrobial properties, are... more Background
Silver nanoparticles (AgNPs), owing to their effective antimicrobial properties, are being widely used in a broad range of applications. These include, but are not limited to, antibacterial materials, the textile industry, cosmetics, coatings of various household appliances and medical devices. Despite their extensive use, little is known about AgNP safety and toxicity vis-à-vis human and animal health. Recent studies have drawn attention towards potential neurotoxic effects of AgNPs, however, the primary cellular and molecular targets of AgNP action/s remain to be defined.
Results
Here we examine the effects of ultra fine scales (20 nm) of AgNPs at various concentrations (1, 5, 10 and 50 µg/ml) on primary rat cortical cell cultures. We found that AgNPs (at 1-50 µg/ml) not only inhibited neurite outgrowth and reduced cell viability of premature neurons and glial cells, but also induced degeneration of neuronal processes of mature neurons. Our immunocytochemistry and confocal microscopy studies further demonstrated that AgNPs induced the loss of cytoskeleton components such as the β-tubulin and filament actin (F-actin). AgNPs also dramatically reduced the number of synaptic clusters of the presynaptic vesicle protein synaptophysin, and the postsynaptic receptor density protein PSD-95. Finally, AgNP exposure also resulted in mitochondria dysfunction in rat cortical cells.
Conclusions
Taken together, our data show that AgNPs induce toxicity in neurons, which involves degradation of cytoskeleton components, perturbations of pre- and postsynaptic proteins, and mitochondrial dysfunction leading to cell death. Our study clearly demonstrates the potential detrimental effects of AgNPs on neuronal development and physiological functions and warns against its prolific usage.
"""Oxidative stress has been suggested as a potential contributor to the development of diabetic... more """Oxidative stress has been suggested as a potential
contributor to the development of diabetic complications. In
this study, we investigated the protective effect of a strong
antioxidant copper complex against streptozotocin (STZ)-induced
diabetes in animals. Out of four copper complexes
used, copper(II) (3,5-diisopropyl salicylate)4 (Cu(II)DIPS)
was found to be the most potent antioxidant.copper complex.
Pretreatment with Cu(II)DIPS (5 mg/kg) twice a week prior to
the injection of streptozotocin (50 mg/kg) has reduced the
level of hyperglycemia by 34 % and the mortality rate by
29 %. Injection of the same dosage of the ligand 3,5-
diisopropyl salicylate has no effect on streptozotocininduced
hyperglycemia. The same copper complex has neither
hypoglycemic activity when injected in normal rats nor
antidiabetic activity when injected in STZ-induced diabetic
rats. The protective effect of Cu(II)DIPS could be related to its
strong antioxidant activity compared to other copper complexes
median effective concentration (MEC)=23.84 ƒÊg/ml
and to Trolox MEC=29.30 ƒÊg/ml. In addition, it reduced
serum 8-hydroxy-2Œ-deoxyguanosine, a biomarker of oxidative
DNA damage, by 29 %. This effect may explain why it
was not effective against diabetic rats, when ƒÀ Langerhans
cells were already destroyed. Similar protective activities were
reported by other antioxidants like Trolox."""
In Parkinson's Disease / Book 4. Pages 165-174. ISBN: 978-953-307-463-4. Edited by Prof. David Finkelstein. Intech Open Access Publisher., 2011
"It has been widely accepted that the degeneration of the dopaminergic neurons within the nigrost... more "It has been widely accepted that the degeneration of the dopaminergic neurons within the nigrostriatal pathway following treatment with the neurotoxin 6-hydroxy dopamine (6-OH-DA) to be used as a good model of Parkinson’s Disease.
This model was used here to investigate the effect of pre-treatment with a glutamate metabotropic receptor agonist Sub-type III, L-2-amino-4-phosphonobutyrate (LAP4) and a glutamate metabotropic receptor antagonist, (RS)-a-methyl-4-phosphono-phenylglycine (MPPG) injected into the nigrostriatal bundle or to the striatum, in-vivo on rats with motor disorders induced by intra-cerebral microinjection of 6-OH-DA using the following coordinates: AP= -1.8 mm, L= ± 1.8 mm and V = - 6.1 mm. This caused the animals to become Parkinsonian with decreases in locomotion and in body weight, and significant increases in rotational movement and rearing. The volume of 2 µL buffer phosphate solution or the same volume of the drugs solution, were slowly micro-injected in a speed of 2 µL per 2 min. to avoid brain damage
The glutamate presynaptic agonist LAP4 was micro-injected unilaterally into the nigrostriatal bundle (the above coordinates), 15 min before injection of 6-OH-DA. LAP4 significantly reduced the motor disorders. Locomotion was increased to normal values from (8.22 ± 1.03 (36) to 16.17 ± 1.46 (18) (P<0.005), the percentage increase in body weight was reversed from 2% to 37%, (P<0.01), while rotation movements were reduced by 35% (P<0.05) after one week and by 61% (P<0.0005) after 4 weeks, while rearing was reduced significantly by 83% (P<0.0005) after one week and 93 % after four weeks (P<0.0005). Pre-treatment with MPPG which was focally micro-injected into the same area, has produced no significant decrease in locomotion produced by 6-OH-DA, and similar effect with rotation and rearing. The only significant activity was observed in body weight which was reduced from 2% to 22%.
Similar changes in locomotion, rotation and rearing were observed when LAP4 was injected to the striatum where using a second cannula which was implanted in the striatum, using the following coordinates: AP= -2.4 mm, L= ± 1.3 mm and V = - 7.8 mm.
These results suggest that agonists of glutamate metabotropic receptors sub-type III, which decrease glutamate release by decreasing Ca++ uptake into presynaptic membranes in glutamatergic neurons in basal ganglia circuits, might prevent development of clinical features of Parkinson's disease."
Journal of Medicinal Food, 2008
Biological Trace Element Research, 2005
In these experiments we have tested the effect of bis(acetato)tetrakis (imidazole) copper(II) on ... more In these experiments we have tested the effect of bis(acetato)tetrakis (imidazole) copper(II) on the release and uptake of 14C-GABA and 3H-glutamate from brain slices and brain cortical synaptosomes. Cu(OAc)2(Im)4 in concentrations ranging from 1 to 100 μM has increased the release of GABA and glutamate from brain slices and synaptosomal preparations in a dose-related manner when the effect on GABA release is two-fold greater than glutamate and 10-fold greater than alanine. Pretreatment with a GABA uptake inhibitor such as 1–2 mM nipecotic acid has no effect on 14C-GABA release, whereas hydroxy aspartate, the glutamate uptake inhibitor, has elevated the stimulated release of glutamate. Copper(II) chloride, the inorganic form of copper, had no significant effect either on GABA release or on glutamate release. The stimulated release of exogenous GABA and glutamate was Ca2+-dependent, because it was inhibited by EGTA, and neuronal, because it was blocked by tetrodotoxin. The recent results can explain the anticonvulsant activity of Cu(OAc)2(Im)4 against strychnine-induced seizures by increasing the net release of GABA from cortical neurons.
Towards New Therapies for Parkinson's Disease, 2011
Biological Trace Element Research, 2013
Acta Biologica Hungarica, 1999
1. The application of the volatile anaesthetics, halothane and isoflurane (1% v/v and 2% v/v), to... more 1. The application of the volatile anaesthetics, halothane and isoflurane (1% v/v and 2% v/v), to the CNS of Lymnaea reduced the firing frequency of the small weakly coupled pedal A cluster (PeA) neurones, which eventually become quiescent. There was no change in their resting membrane potential. 2. Met-enkephalin significantly increased the coupling coefficient between PeA neurones. 3. The volatile anaesthetics decreased the coupling coefficient even in the presence of met-enkephalin. 4. These effects were dose dependent and the effects of halothane were more rapid than those of isoflurane, reflecting their different anaesthetic potencies.
There is a substantial emerging literature on the complexity and plasticity of the apparently sim... more There is a substantial emerging literature on the complexity and plasticity of the apparently simple electrical synapses [ES]. Here we draw attention to some of the most recent findings in this rapidly evolving field. • ES are ubiquitous, found in all multicellular animals and structurally underlain by gap junctions. Gap junctions are topographically similar in vertebrates and invertebrates, but based on different mutually exclusive connexins and innexins respectively. • It is now clear that ES may be modulated and exhibit plasticity in addition to promoting synergy between coupled neurons according to the strength of coupling. Strong electrical coupling promotes synchronous activity while weak coupling may desynchronise coupled neurons. • Chemical synapses may modulate ES conductances and may regulate the degree of coupling between neurons. Because ES act as low pass filters, prolonged spike after-hyperpolarisations can allow them to act as inhibitory connections, but modifications...
The actions of clinical concentrations of volatile anaesthetic halothane and isoflurane were comp... more The actions of clinical concentrations of volatile anaesthetic halothane and isoflurane were compared with those of pentobarbitone on identified neurons of the pond snail Lymnaea stagnalis. Application of halothane and isoflurane (1% v/v and 2% v/v), to the CNS of Lymnaea caused the strongly electrically coupled neurons VD1 and RPD2 to become quiescent, with a significant increase in membrane potential and a significant reduction in their coupling coefficient. These results clearly demonstrate that the volatile anaesthetics and barbiturates have different mechanisms of action at electrical synapses. The effects of volatile anaesthetics were dose dependent, and the actions of halothane were more rapid than those of isoflurane, reflecting their different anaesthetic potencies. Sodium-pentobarbitone had markedly different effects from the volatile anaesthetics. Clinical concentrations of pentobarbitone (100 ± M) caused VD1 and RPD2 to become quiescent with no significant change in eith...
Phthalate esters are industrial chemicals widely used in cosmetics, plastics bottles and medical ... more Phthalate esters are industrial chemicals widely used in cosmetics, plastics bottles and medical devices, and the risk of exposure to phthalates is on the increase. In recent years, many studies have been carried out on the possible health hazards of phthalates, including the effect on reproduction. In this study rats were injected twice weekly with Di-butyl Phthalates (DBP) or Di (2-Ethylhexyl) Phthalates (DEHP) (100 mg/kg) and cohabited with male rats for one month. Fertility and mortality rates as well as fecundity were impacted significantly. Fertility rate decreased from 87 % in control rsats to 67 % in DBP treated and 50 % in DEHP treated rats. Similarly mortality rate in new born litters increased from 2.8 % in control rats to 52.3 % in DBP treated and 31.3 % in DEHP treated rats. Fecundity rate which expresses the average number of litters in each delivery was reduced from 8.2 in control rats to 7.3 in DBP treated and 5.3 in DEHP treated rats. No significant changes were obs...
Frontiers in Physiology, May 31, 2019
Differential effects of volatile general anaesthetics and sodium pentobarbital on input resistanc... more Differential effects of volatile general anaesthetics and sodium pentobarbital on input resistance [R m ], membrane time constant [ m ] and capacitance [C m ] of VD1 and RPD2 neurons of Lymnaea are reported in this paper. The volatile anaesthetics halothane and isoflurane caused a significant reduction in the input resistance, membrane time constant and capacitance in a dose dependent manner and halothane was more potent than isoflurane. The clinical concentration [100 M] of pentobarbitone caused no change in R m , m and C m of VD1 and RPD2, whereas 2.0 and 0.5 mM pentobarbitone increased them significantly during phase I but caused no change in these parameters during phase II.
Biological Trace Element Research
In these experiments we have tested the effect of bis(acetato)tetrakis (imidazole) copper(II) on ... more In these experiments we have tested the effect of bis(acetato)tetrakis (imidazole) copper(II) on the release and uptake of 14C-GABA and 3H-glutamate from brain slices and brain cortical synaptosomes. Cu(OAc)2(Im)4 in concentrations ranging from 1 to 100 microM has increased the release of GABA and glutamate from brain slices and synaptosomal preparations in a dose-related manner when the effect on GABA release is two-fold greater than glutamate and 10-fold greater than alanine. Pretreatment with a GABA uptake inhibitor such as 1-2 mM nipecotic acid has no effect on 14C-GABA release, whereas hydroxy aspartate, the glutamate uptake inhibitor, has elevated the stimulated release of glutamate. Copper(II) chloride, the inorganic form of copper, had no significant effect either on GABA release or on glutamate release. The stimulated release of exogenous GABA and glutamate was Ca2+-dependent, because it was inhibited by EGTA, and neuronal, because it was blocked by tetrodotoxin. The recent...
Molecular Brain, 2016
Concerns have risen regarding the potential side effects of clinical exposure of the pediatric po... more Concerns have risen regarding the potential side effects of clinical exposure of the pediatric population to inhalational anesthetics, and how they might impact cognitive, learning, and memory functions. However, neither the mechanisms of anesthetic cytotoxicity, nor potential protective strategies, have yet been fully explored. In this study, we examined whether two of the most commonly used inhalational anesthetics, sevoflurane and desflurane, affect neuronal viability and synaptic network assembly between cultured rat cortical neurons. Primary rat cortical neuron cultures were exposed to equipotent sevoflurane or desflurane for 1 hour. Neuron viability, synaptic protein expression, mitochondrial morphology, and neurite growth were assayed with immunostaining and confocal microscopy techniques. The effects of anesthetics on the functional development of neural networks were evaluated with whole-cell patch clamp recordings of spontaneous synaptic currents. Our results demonstrate that an acute exposure to sevoflurane and desflurane inhibits the development of neurite processes, impacts the mitochondria, and compromises synaptic proteins - concomitant with a reduction in synaptic function in mature networks. Interestingly, pretreatment of neurons with a mitochondrial division inhibitor (Mdivi-1) not only protected mitochondria integrity but also played a protective role against anesthetic-induced structural and functional neurotoxicity. We show that Mdivi-1 likely plays a protective role against certain harmful effects of general anesthetics on primary rat neuronal cultures. In addition, Mdivi-1 alone plays a direct role in enhancing growth and modulating synaptic activity. This study highlights the importance of further study into possible protective agents against anesthetic neurotoxicity.
Journal of environmental biology / Academy of Environmental Biology, India, 2014
In the present work, the effect of exposure to cigarette smoke on male fertility in rats, as char... more In the present work, the effect of exposure to cigarette smoke on male fertility in rats, as characterized by changes in the relative weight of sex organs, epididymal sperm count, activity of marker enzymes and DNA damage was evaluated. Exposure of rats to cigarette smoke caused a gradual decrease in total body weight gain and relative weight of the epididymis and seminal vesicles by 30 and 40% respectively. Epididymal sperm count was reduced significantly by 25% (P 0.05) after 2 weeks and by 41% (P 0.001) after 4 weeks of exposure. Exposure to cigarette smoke had reduced the activity of sorbitol dehydogenase by 18% (P < or = 0.05) and increased the activity of lactate dehydrogenase by 28% (P < or = 0.05). The changes in both key enzymes were significant, which reflected the inhibitory effect of cigarette smoke on spermatogenesis and sperm maturation. The toxic effect of exposure could be explained partially due to induction of DNA damage and oxidative stress as shown by the s...
Background Silver nanoparticles (AgNPs), owing to their effective antimicrobial properties, are... more Background
Silver nanoparticles (AgNPs), owing to their effective antimicrobial properties, are being widely used in a broad range of applications. These include, but are not limited to, antibacterial materials, the textile industry, cosmetics, coatings of various household appliances and medical devices. Despite their extensive use, little is known about AgNP safety and toxicity vis-à-vis human and animal health. Recent studies have drawn attention towards potential neurotoxic effects of AgNPs, however, the primary cellular and molecular targets of AgNP action/s remain to be defined.
Results
Here we examine the effects of ultra fine scales (20 nm) of AgNPs at various concentrations (1, 5, 10 and 50 µg/ml) on primary rat cortical cell cultures. We found that AgNPs (at 1-50 µg/ml) not only inhibited neurite outgrowth and reduced cell viability of premature neurons and glial cells, but also induced degeneration of neuronal processes of mature neurons. Our immunocytochemistry and confocal microscopy studies further demonstrated that AgNPs induced the loss of cytoskeleton components such as the β-tubulin and filament actin (F-actin). AgNPs also dramatically reduced the number of synaptic clusters of the presynaptic vesicle protein synaptophysin, and the postsynaptic receptor density protein PSD-95. Finally, AgNP exposure also resulted in mitochondria dysfunction in rat cortical cells.
Conclusions
Taken together, our data show that AgNPs induce toxicity in neurons, which involves degradation of cytoskeleton components, perturbations of pre- and postsynaptic proteins, and mitochondrial dysfunction leading to cell death. Our study clearly demonstrates the potential detrimental effects of AgNPs on neuronal development and physiological functions and warns against its prolific usage.
"""Oxidative stress has been suggested as a potential contributor to the development of diabetic... more """Oxidative stress has been suggested as a potential
contributor to the development of diabetic complications. In
this study, we investigated the protective effect of a strong
antioxidant copper complex against streptozotocin (STZ)-induced
diabetes in animals. Out of four copper complexes
used, copper(II) (3,5-diisopropyl salicylate)4 (Cu(II)DIPS)
was found to be the most potent antioxidant.copper complex.
Pretreatment with Cu(II)DIPS (5 mg/kg) twice a week prior to
the injection of streptozotocin (50 mg/kg) has reduced the
level of hyperglycemia by 34 % and the mortality rate by
29 %. Injection of the same dosage of the ligand 3,5-
diisopropyl salicylate has no effect on streptozotocininduced
hyperglycemia. The same copper complex has neither
hypoglycemic activity when injected in normal rats nor
antidiabetic activity when injected in STZ-induced diabetic
rats. The protective effect of Cu(II)DIPS could be related to its
strong antioxidant activity compared to other copper complexes
median effective concentration (MEC)=23.84 ƒÊg/ml
and to Trolox MEC=29.30 ƒÊg/ml. In addition, it reduced
serum 8-hydroxy-2Œ-deoxyguanosine, a biomarker of oxidative
DNA damage, by 29 %. This effect may explain why it
was not effective against diabetic rats, when ƒÀ Langerhans
cells were already destroyed. Similar protective activities were
reported by other antioxidants like Trolox."""
In Parkinson's Disease / Book 4. Pages 165-174. ISBN: 978-953-307-463-4. Edited by Prof. David Finkelstein. Intech Open Access Publisher., 2011
"It has been widely accepted that the degeneration of the dopaminergic neurons within the nigrost... more "It has been widely accepted that the degeneration of the dopaminergic neurons within the nigrostriatal pathway following treatment with the neurotoxin 6-hydroxy dopamine (6-OH-DA) to be used as a good model of Parkinson’s Disease.
This model was used here to investigate the effect of pre-treatment with a glutamate metabotropic receptor agonist Sub-type III, L-2-amino-4-phosphonobutyrate (LAP4) and a glutamate metabotropic receptor antagonist, (RS)-a-methyl-4-phosphono-phenylglycine (MPPG) injected into the nigrostriatal bundle or to the striatum, in-vivo on rats with motor disorders induced by intra-cerebral microinjection of 6-OH-DA using the following coordinates: AP= -1.8 mm, L= ± 1.8 mm and V = - 6.1 mm. This caused the animals to become Parkinsonian with decreases in locomotion and in body weight, and significant increases in rotational movement and rearing. The volume of 2 µL buffer phosphate solution or the same volume of the drugs solution, were slowly micro-injected in a speed of 2 µL per 2 min. to avoid brain damage
The glutamate presynaptic agonist LAP4 was micro-injected unilaterally into the nigrostriatal bundle (the above coordinates), 15 min before injection of 6-OH-DA. LAP4 significantly reduced the motor disorders. Locomotion was increased to normal values from (8.22 ± 1.03 (36) to 16.17 ± 1.46 (18) (P<0.005), the percentage increase in body weight was reversed from 2% to 37%, (P<0.01), while rotation movements were reduced by 35% (P<0.05) after one week and by 61% (P<0.0005) after 4 weeks, while rearing was reduced significantly by 83% (P<0.0005) after one week and 93 % after four weeks (P<0.0005). Pre-treatment with MPPG which was focally micro-injected into the same area, has produced no significant decrease in locomotion produced by 6-OH-DA, and similar effect with rotation and rearing. The only significant activity was observed in body weight which was reduced from 2% to 22%.
Similar changes in locomotion, rotation and rearing were observed when LAP4 was injected to the striatum where using a second cannula which was implanted in the striatum, using the following coordinates: AP= -2.4 mm, L= ± 1.3 mm and V = - 7.8 mm.
These results suggest that agonists of glutamate metabotropic receptors sub-type III, which decrease glutamate release by decreasing Ca++ uptake into presynaptic membranes in glutamatergic neurons in basal ganglia circuits, might prevent development of clinical features of Parkinson's disease."
Journal of Medicinal Food, 2008
Biological Trace Element Research, 2005
In these experiments we have tested the effect of bis(acetato)tetrakis (imidazole) copper(II) on ... more In these experiments we have tested the effect of bis(acetato)tetrakis (imidazole) copper(II) on the release and uptake of 14C-GABA and 3H-glutamate from brain slices and brain cortical synaptosomes. Cu(OAc)2(Im)4 in concentrations ranging from 1 to 100 μM has increased the release of GABA and glutamate from brain slices and synaptosomal preparations in a dose-related manner when the effect on GABA release is two-fold greater than glutamate and 10-fold greater than alanine. Pretreatment with a GABA uptake inhibitor such as 1–2 mM nipecotic acid has no effect on 14C-GABA release, whereas hydroxy aspartate, the glutamate uptake inhibitor, has elevated the stimulated release of glutamate. Copper(II) chloride, the inorganic form of copper, had no significant effect either on GABA release or on glutamate release. The stimulated release of exogenous GABA and glutamate was Ca2+-dependent, because it was inhibited by EGTA, and neuronal, because it was blocked by tetrodotoxin. The recent results can explain the anticonvulsant activity of Cu(OAc)2(Im)4 against strychnine-induced seizures by increasing the net release of GABA from cortical neurons.
Biological Trace Element Research, 2004
The anticonvulsant activity of bis(acetato)tetrakis(imidazole) copper(II), Cu(OAc)2(Im)4, was stu... more The anticonvulsant activity of bis(acetato)tetrakis(imidazole) copper(II), Cu(OAc)2(Im)4, was studied in normal mice using chemical convulsions induced by strychnine, thiosemicarbazide, picrotoxin, and pentelenetetrazol. Intraperitoneal administration of Cu(OAc) 2(Im)4, 50 mg/kg body mass, has delayed the onset of strychnine (3 mg/kg)-induced convulsion by 204% (p≤0.005) and thiosemicarbazide (20 mg/kg)-induced convulsant by 61% (p≤0.005). The changes in the onset of picrotoxin-(6 mg/kg) and pentelenetetrazol (50 mg/kg)-induced convulsions were not significant. The same dosage of the copper compound was effective in delaying the lethal time and reducing the mortality rate of treated animals. The anticonvulsant activity of Cu(OAc) 2(Im)4 complex against strychnine was not related to its constituents because the inorganic form of copper such as copper chloride, copper acetate, and the parent imidazole has no anticonvulsant activity. Other copper(II) complexes like copper(II)aspirinate and bis(acetato)bis(2-methyl imidazole) copper(II) were less effective.