Most Cited Article: Citrus Peel Extract Attenuates Acute Cyanide Poisoning-Induced Seizures and Oxidative Stress in Rats

Citrus Peel Extract Attenuates Acute Cyanide Poisoning-Induced Seizures and Oxidative Stress in Rats


Author(s):

Ahmed E. Abdel MoneimPages 638-646 (9)


Abstract:


The primary aimed of this study was to investigate the potential protective effects of methanolic extract of citrus peel (MECP) on acute cyanide (KCN) poisoning-induced seizures and oxidative stress in rats. The intraperitoneal LD50 value of KCN (6.3 mg/Kg bwt), based on 24 hrs mortality, was significantly increased by 9, 52 or 113% by oral administration of MECP (500 mg/Kg bwt) pre-administered for 1, 2 and 3 days, respectively, in rats in a time-dependent manner. Intraperitoneal injection of the sublethal dose of KCN (3 mg/Kg bwt) into rats increased, 24 hrs later, lipid peroxidation (LPO), nitric oxide (NO), glutamate levels and acetylcholinesterase (AChE) activity in hippocampus, striatum and cerebral cortex. KCN also decreased brain glutathione (GSH) level and superoxide dismutase (SOD) and catalase (CAT) activities in these animals. Pre-treatment of rats with MECP inhibited KCN-induced increases in LPO, NO, and glutamate levels and AChE activity as well as decreases in brain GSH level and SOD and CAT activities. In addition, KCN significantly decreased norepinephrine, dopamine and serotonin levels in different brain regions which were resolved by MECP. From the present results, it can be concluded that the neuroprotective effects of MECP against KCN-induced seizures and oxidative stress may be due to the inhibition of oxidative stress overproduction and maintenance of antioxidant defense mechanisms.

Keywords:

Antioxidants, citrus peel, oxidative stress, potassium cyanide, seizures.


Affiliation:

Department of Zoology and Entomology, Faculty of Science, Helwan University, 11795 Helwan, Cairo, Egypt.

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New Issue ::: CNS & Neurological Disorders – Drug Targets, 15 Issue 6

CNS & Neurological Disorders – Drug Targets aims to cover all the latest and outstanding developments on the medicinal chemistry, pharmacology, molecular biology, genomics and biochemistry of contemporary molecular targets involved in neurological and central nervous system (CNS) disorders e.g. disease specific proteins, receptors, enzymes, genes.

CNS & Neurological Disorders – Drug Targets publishes guest edited thematic issues written by leaders in the field covering a range of current topics of CNS & neurological drug targets. The journal also accepts for publication original research articles, letters, reviews and drug clinical trial studies.

As the discovery, identification, characterization and validation of novel human drug targets for neurological and CNS drug discovery continues to grow; this journal is essential reading for all pharmaceutical scientists involved in drug discovery and development.

Articles from the journal CNS & Neurological Disorders – Drug Targets, 15 Issue 6

• Commentary: Histaminergic Drugs Could be Novel Targets for Neuroprotection in CNS Disorders
• Conference Report: 14th International Congress on Amino Acids, Peptides and Proteins, Vienna, Austria, August 3-7, 2015
• Editorial (Thematic Issue: Old Facts and New Perspectives to Face Alzheimer’s Dementia. Focus on Non Neuronal Participants to Neurodegeneration)
• Targeting New Pharmacological Approaches for Alzheimer’s Disease: Potential for Statins and Phosphodiesterase Inhibitors
• Insulin and the Future Treatment of Alzheimer’s Disease
• Adrenergic Drugs Blockers or Enhancers for Cognitive Decline ? What to Choose for Alzheimer’s Disease Patients?
• Emerging Risk Factors for Dementia: The Role of Blood Pressure Variability
• Obstructive Sleep Apnea Syndrome: An Emerging Risk Factor for Dementia
• Beyond Cholinesterase Inhibition: Anti-Inflammatory Role and Pharmacological Profile of Current Drug Therapy for Alzheimer’s Disease
• Influence of Hypertension, Alone and in Combination with Other Vascular Risk Factors on Cognition
• NLRP3 Is Involved in Ischemia/Reperfusion Injury
• Neurobiology of Bipolar Disorder: Abnormalities on Cognitive and Cortical Functioning and Biomarker Levels
• Decreased Expression of Sox-1 in Cerebellum of Rat with Generalized Seizures Induced by Kindling Model
• Preliminary Pharmacological Screening of Some Thiosemicarbazide, s-triazole, and Thiadiazole Derivatives
• Vertical and Horizontal Convergences of Targeting Pathways in Combination Therapy with Baicalin and Jasminoidin for Cerebral Ischemia

For details on the articles, please visit this link :: http://bit.ly/2aYehrv

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Scholarly Publications by Japanese Authors in BSP Journal: CNS & Neurological Disorders – Drug Targets

CNS & Neurological Disorders – Drug TargetsImage

– Biosynthetic Pathways of Bioactive N-Acylethanolamines in Brain

Author(s): Kazuhito Tsuboi, Natsuki Ikematsu, Toru Uyama, Dale G. Deutsch, Akira Tokumura and Natsuo Ueda


Affiliation: Department of Biochemistry, Kagawa University School of Medicine, 1750-1 Ikenobe, Miki, Kagawa 761-0793, Japan.


Abstract

Ethanolamides of long-chain fatty acids are a class of endogenous lipid mediators generally referred to as Nacylethanolamines (NAEs). NAEs include anti-inflammatory and analgesic palmitoylethanolamide, anorexic oleoylethanolamide, and the endocannabinoid anandamide. Since the endogenous levels of NAEs are principally regulated by enzymes responsible for their biosynthesis and degradation, these enzymes are expected as targets for the development of therapeutic agents. Thus, a better understanding of these enzymes is indispensable. The classic “N-acylationphosphodiesterase pathway” for NAE biosynthesis is composed of two steps; the formation of Nacylphosphatidylethanolamine (NAPE) by N-acyltransferase and the release of NAE from NAPE by NAPE-hydrolyzing phospholipase D (NAPE-PLD). However, recent studies, including the analysis of NAPE-PLD-deficient (NAPE-PLD-/-) mice, revealed the presence of NAPE-PLD-independent multi-step pathways to form NAEs from NAPE in animal tissues. Our recent studies using NAPE-PLD-/- mice also suggest that NAE is formed not only from NAPE, but also from Nacylated plasmalogen-type ethanolamine phospholipid (N-acyl-plasmenylethanolamine) through both NAPE-PLDdependent and -independent pathways. Here, we present recent findings on NAE biosynthetic pathways mainly occurring in the brain.

– Improving the Treatment of Schizophrenia: Role of 5-HT Receptors in Modulating Cognitive and Extrapyramidal Motor Functions

Author(s): Saki Shimizu, Yuto Mizuguchi and Yukihiro Ohno

Affiliation: Laboratory of Pharmacology, OsakaUniversity of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan.

Abstract

Patients with schizophrenia exhibit various clinical symptoms including positive and negative symptoms, neurocognitive impairments and mood disturbances. Although a series of second generation antipsychotics (SGAs) (e.g., risperidone, olanzapine and quetiapine) have been developed in the past two decades, clinical reports do not necessarily show advantages over first generation antipsychotics (FGAs) in the treatment of schizophrenia, especially in their efficacy against cognitive impairment and ability to cause extrapyramidal side effects (EPS). Recently, several lines of studies have revealed therapeutic roles of 5-HT receptors in modulating cognitive impairments and extrapyramidal motor disorders. Specifically, inhibition of 5-HT1A, 5-HT3 and 5-HT6 receptors or activation of 5-HT4 receptors alleviates cognitive impairments (e.g., deficits in learning and memory). In addition, stimulation of 5-HT1A receptors or inhibition of 5-HT3and 5-HT6 receptors as well as 5-HT2A/2C receptors can ameliorate extrapyramidal motor disorders. Thus, controlling the activity of 5-HT1A, 5-HT3 or 5-HT6receptors seems to provide benefits by both alleviating cognitive impairments and reducing antipsychotic-induced EPS. This article reviews the functional roles and mechanisms of 5-HT receptors in the treatment of schizophrenia, focusing on the serotonergic modulation of cognitive and extrapyramidal motor functions, and illustrates future therapeutic strategies.

– Beyond Rodent Models of Pain: Non-Human Primate Models for Evaluating Novel Analgesic Therapeutics and Elaborating Pain Mechanisms


Author(s): Aldric T. Hama, Katsuo Toide and Hiroyuki Takamatsu


Affiliation: Hamamatsu Pharma Research, Kita-ku, 1-3-7 Shinmiyakoda, Hamamatsu 431-2103, Japan.


Abstract

Evaluation of potential analgesic therapeutics and the elaboration of the neurobiology of pain have heavily relied on pain models developed in rodents. However, a limitation of rodents is their phylogenetic distance from humans, which could in part account for the failure of some preclinical findings to translate to clinical utility. By contrast, given their genetic closeness and phenotypic similarities to humans, it is suggested that there be greater utilization of non-human primates (NHP) in preclinical pain studies. Methods to induce chronic pain-like states and quantify changes in nociception that have been developed in rodents could be adapted to the NHP. Similarly, human experimental injury-induced sensitization, which attempts to temporarily mimic the neuropathology and symptoms observed in the chronic pain state, could be adapted to the NHP. The NHP could then serve as a platform to validate human experimental models as well as proof-of-concept studies. Beyond experimentally modeled pain states, a number of naturally occurring disease states, such as osteoarthritis, are expressed by NHP, which could be utilized for both hypothesis testing and proof-of-concept studies. While NHP studies are logistically cumbersome, it is envisioned that NHP pain models will add value to current preclinical data and greatly facilitate the discovery of novel analgesic treatments.

Courtesy by Bentham Insight

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Scholarly Publications by Japanese Authors in BSP Journal: CNS & Neurological Disorders – Drug Targets

CNS & Neurological Disorders – Drug TargetsImage

– Biosynthetic Pathways of Bioactive N-Acylethanolamines in Brain

Author(s): Kazuhito Tsuboi, Natsuki Ikematsu, Toru Uyama, Dale G. Deutsch, Akira Tokumura and Natsuo Ueda


Affiliation: Department of Biochemistry, Kagawa University School of Medicine, 1750-1 Ikenobe, Miki, Kagawa 761-0793, Japan.


Abstract

Ethanolamides of long-chain fatty acids are a class of endogenous lipid mediators generally referred to as Nacylethanolamines (NAEs). NAEs include anti-inflammatory and analgesic palmitoylethanolamide, anorexic oleoylethanolamide, and the endocannabinoid anandamide. Since the endogenous levels of NAEs are principally regulated by enzymes responsible for their biosynthesis and degradation, these enzymes are expected as targets for the development of therapeutic agents. Thus, a better understanding of these enzymes is indispensable. The classic “N-acylationphosphodiesterase pathway” for NAE biosynthesis is composed of two steps; the formation of Nacylphosphatidylethanolamine (NAPE) by N-acyltransferase and the release of NAE from NAPE by NAPE-hydrolyzing phospholipase D (NAPE-PLD). However, recent studies, including the analysis of NAPE-PLD-deficient (NAPE-PLD-/-) mice, revealed the presence of NAPE-PLD-independent multi-step pathways to form NAEs from NAPE in animal tissues. Our recent studies using NAPE-PLD-/- mice also suggest that NAE is formed not only from NAPE, but also from Nacylated plasmalogen-type ethanolamine phospholipid (N-acyl-plasmenylethanolamine) through both NAPE-PLDdependent and -independent pathways. Here, we present recent findings on NAE biosynthetic pathways mainly occurring in the brain.

– Improving the Treatment of Schizophrenia: Role of 5-HT Receptors in Modulating Cognitive and Extrapyramidal Motor Functions

Author(s): Saki Shimizu, Yuto Mizuguchi and Yukihiro Ohno

Affiliation: Laboratory of Pharmacology, OsakaUniversity of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan.

Abstract

Patients with schizophrenia exhibit various clinical symptoms including positive and negative symptoms, neurocognitive impairments and mood disturbances. Although a series of second generation antipsychotics (SGAs) (e.g., risperidone, olanzapine and quetiapine) have been developed in the past two decades, clinical reports do not necessarily show advantages over first generation antipsychotics (FGAs) in the treatment of schizophrenia, especially in their efficacy against cognitive impairment and ability to cause extrapyramidal side effects (EPS). Recently, several lines of studies have revealed therapeutic roles of 5-HT receptors in modulating cognitive impairments and extrapyramidal motor disorders. Specifically, inhibition of 5-HT1A, 5-HT3 and 5-HT6 receptors or activation of 5-HT4 receptors alleviates cognitive impairments (e.g., deficits in learning and memory). In addition, stimulation of 5-HT1A receptors or inhibition of 5-HT3and 5-HT6 receptors as well as 5-HT2A/2C receptors can ameliorate extrapyramidal motor disorders. Thus, controlling the activity of 5-HT1A, 5-HT3 or 5-HT6receptors seems to provide benefits by both alleviating cognitive impairments and reducing antipsychotic-induced EPS. This article reviews the functional roles and mechanisms of 5-HT receptors in the treatment of schizophrenia, focusing on the serotonergic modulation of cognitive and extrapyramidal motor functions, and illustrates future therapeutic strategies.

– Beyond Rodent Models of Pain: Non-Human Primate Models for Evaluating Novel Analgesic Therapeutics and Elaborating Pain Mechanisms


Author(s): Aldric T. Hama, Katsuo Toide and Hiroyuki Takamatsu


Affiliation: Hamamatsu Pharma Research, Kita-ku, 1-3-7 Shinmiyakoda, Hamamatsu 431-2103, Japan.


Abstract

Evaluation of potential analgesic therapeutics and the elaboration of the neurobiology of pain have heavily relied on pain models developed in rodents. However, a limitation of rodents is their phylogenetic distance from humans, which could in part account for the failure of some preclinical findings to translate to clinical utility. By contrast, given their genetic closeness and phenotypic similarities to humans, it is suggested that there be greater utilization of non-human primates (NHP) in preclinical pain studies. Methods to induce chronic pain-like states and quantify changes in nociception that have been developed in rodents could be adapted to the NHP. Similarly, human experimental injury-induced sensitization, which attempts to temporarily mimic the neuropathology and symptoms observed in the chronic pain state, could be adapted to the NHP. The NHP could then serve as a platform to validate human experimental models as well as proof-of-concept studies. Beyond experimentally modeled pain states, a number of naturally occurring disease states, such as osteoarthritis, are expressed by NHP, which could be utilized for both hypothesis testing and proof-of-concept studies. While NHP studies are logistically cumbersome, it is envisioned that NHP pain models will add value to current preclinical data and greatly facilitate the discovery of novel analgesic treatments.

Courtesy by Bentham Insight

Read More

Highlighted Article Flyer for the journal “CNS & Neurological Disorders – Drug Targets”

courtesy by: Bentham Insight

Read More