Omar M.E. Abdel-Salam

The effect of different antidepressant drugs of oxidative stress after lipopolysaccharide administration in mice

This study investigated the effect of the serotonin selective reuptake inhibitors (SSRIs) fluoxetine, sertraline, fluvoxamine and the tricyclic antidepressant (TCA) impiramine on oxidative stress in brain and liver induced by lipopolysaccharide administration in mice. Each drug was administered subcutaneously at doses of 10 or 20 mg/kg, for two days prior to intraperitoneal (i.p.) administration of lipopolysaccharide E (LPS: 200 µg/kg). Mice were euthanized 4 h after administration of the lipopolysaccharide. Lipid peroxidation (malondialdehyde; MDA), reduced glutathione (GSH) and nitric oxide (nitrite/nitrate) concentrations were measured in brain and liver. Results: The administration of lipopolysaccharide increased oxidative stress in brain and liver; it increased brain MDA by 36.1 and liver MDA by 159.8 %. GSH decreased by 34.1 % and 64.8 % and nitric oxide increased by 78.7 % and 103.8 % in brain and liver, respectively. In brain, MDA decreased after the administration of sertraline and by the lower dose of fluoxetine or fluvoxamine, but increased after the higher dose of imipramine. Reduced glutathione increased after sertraline, fluvoxamine and the lower dose of fluoxetine or imipramine. Nitric oxide decreased by sertraline, fluoxetine, fluvoxamine and by the lower dose of imipramine. In the liver, all drugs decreased MDA and increased GSH level. Nitric oxide is decreased by sertraline, fluvoxamine and by the lower dose of fluoxetine or imipramine. It is concluded that, during mild systemic inflammatory illness induced by peripheral bacterial endotoxin injection, the SSRIs fluoxetine, sertraline and fluvoxamine reduced, while the TCA impiramine increased oxidative stress induced in the brain. The SSRIs as well as imipramine reduced oxidative stress due to lipopolysaccharide in liver tissue.

Cerebrolysin protects against rotenone-induced oxidative stress and neurodegeneration

License. The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. Permissions beyond the scope of the License are administered by Dove Medical Press Limited. Information on how to request permission may be found at: http://www.dovepress.com/permissions.php Journal of Neurorestoratology 2014:2 47–63 Journal of Neurorestoratology Dovepress

Neuroprotection by Montelukast against Rotenone-Induced Rat Brain Damage

Montelukast is a cysteinyl-leukotriene receptor antagonist used in asthma prophylaxis. In this study, the effect of montelukast (10 or 20 mg/kg) on neuronal damage and oxidative stress induced in the rat brain by rotenone was examined. Rats were treated with rotenone subcutaneously at 1.5 mg/kg every other day alone or along with montelukast. The control group received the vehicle dimethyl sulfoxide (DMSO). The results showed that compared with the vehicle-treated group, rotenone resulted in increased brain lipid peroxidation by 84.5% as assessed by malondialdehyde (MDA) content. Nitric oxide increased by 77.4% while reduced glutathione (GSH) and total antioxidant capacity (TAC) decreased by 37.7% and 68.6%, respectively. In addition, the activities of superoxide dismutase (SOD), paraoxonase-1 (PON-1), and butyrylcholinesterase (BChE) significantly decreased by 34.6%, 68%, and 75.2%, respectively, after rotenone injection. Rotenone caused neurodegenerative changes in the cerebral cortex and substantia nigra. The administration of montelukast along with rotenone decreased MDA by 34.1–53.6%, nitric oxide by 51.6–64.7%, increased GSH content by 20.7–65.8%, and increased TAC by 109.6–156.2%. SOD activity increased by 50–62.5%, PON-1 activity by 161.1–203.7%, and BChE activity by 135.3–274.3% compared with respective rotenone control values. The rotenone-induced neuronal damage was ameliorated dose-dependently by montelukast. These results indicate that montelukast exerts a neuroprotective effect in the rotenone model of neurotoxicity. The neuroprotective action of montelukast is likely to involve an inhibitory effect on oxidative stress and nitric oxide. It is suggested that montelukast could be of value in the adjunctive treatment of Parkinson’s disease.

Citric Acid an Antioxidant in Liver

Abstract Citric acid is a weak organic acid found in many fruits and is used as preservative in human food being an antioxidant. Inside the cell, citric acid plays an important role in the intermediary metabolism, being a component of the tricarboxylic acid cycle or Krebs cycle. Our studies performed in rodents indicated that the administration of citric acid was able to protect the liver tissue against the deleterious effects of carbon tetrachloride (CCl4), lipopolysaccharide endotoxin (LPS), or the organophosphorus insecticide malathion minimizing both the leakage of hepatocellular enzymes alanine aminotransferase and aspartate aminotransferase into plasma and the extent of histological damage as well. Metabolic perturbations due to CCl4, such as the decrease in mucopolysaccharides, and proteins in hepatocytes were reduced by citric acid. The increase in the oxidative stress marker malondialdehyde, and the depletion of reduced glutathione in liver of malathion-treated rats and the decline in hepatic glutathione peroxidase activity in mice treated with LPS were alleviated by citric acid. These biochemical changes occurred along with inhibition of activated caspase-3 and inducible nitric oxide synthase (iNOS) expression in the liver tissue. Our observations suggest that citrate exerts an antioxidant action limiting excessive generation of reactive oxygen/nitrogen metabolites. The aim of this chapter is to review the role of free radicals in liver diseases, summarize the results of our experiments and to discuss available data pertaining to protective effects for citric acid in other tissues and the possible mechanisms involved.

Capsicum Protects Against Rotenone-Induced Toxicity in Mice Brain Via Reduced Oxidative Stress and 5-Lipoxygenase Activation

Objective: Is to investigate the effect of Capsicum annuum L extract for its ability to prevent neuronal degeneration in rotenone intoxicated mice. Methods: Rotenone 1.5 mg/kg was subcutaneously given three times per week for two consecutive weeks. Starting from the first day of rotenone treatment, mice also received intraperitoneal injections of Capsicum extract (56 or 224 mg/kg). The brain and liver content of the lipid peroxidation product malondialdehyde (MDA), nitric oxide, reduced glutathione (GSH), paraoxonase 1 activity as well as brain cholinesterase and 5-lipoxygenase activities were determined. Histopathology and glial fibrillary acidic protein (GFAP) immunostaining in brain were also performed. Results: Rotenone treatment caused significantly raised brain and liver MDA by 64.4% and 93.3% and nitric oxide by 77.8% and 40.3%, respectively. Reduced glutathione decreased by 45.4% and 24.3% and PON1 activity fell by 39.4% and 28.7% in both the brain and liver, respectively. Cholinesterase activity in brain was inhibited by 60.6% while 5-lipoxygenase increased by 38.9%. In brain tissue, Capsicum prevented the increase in MDA and nitric oxide levels. Capsicum also restored GSH, PON-1 activity and alleviated the increase in 5-lipoxygenase activity. Cholinesterase activity was almost restored to control value by the higher dose of Capsicum. In the liver tissue, Capsicum caused a significant decrease in MDA, and nitric oxide levels, and increased GSH. It also increased PON-1 activity. The neurotoxicity of rotenone was prevented by the administration of Capsicum extract which prevented the neuronal degeneration and restored GFAP positive cells. Conclusions: Capsicum exerts a neuroprotective effect in rotenone intoxicated mice and this is likely to involve reduced oxidative stress and 5-lipoxygenase activation.

Cerebrolysin attenuates oxidative stress and neurodegeneration in acute malathion toxicity in the rat

Neurotoxicity caused by organophosphate insecticides in a recognized health problem [1]. These agents are widely used in agriculture, veterinary and in the household [2]. Acute toxicity is largely due to excessive cholinergic activity [3]. Organophosphates bind to and inhibit the cholinesterases; acetylcholinesterase (EC 3.1.1.7; AChE) and butyrylcholinesterase (EC 3.1.1.8’ BChE). In the central and peripheral nervous system, acetylcholinesterase (AChE) is the enzyme that hydrolyzes the neurotransmitter acetylcholine (ACh), thereby, terminating its action at the cholinergic synapse [4]. Organophosphates thus cause the accumulation of ACh in the synaptic cleft and over stimulation of the cholinergic receptors at postsynaptic cells and/or end organs, and the development of signs of acute toxicity such as excessive salivation, lacrimation, bradycardia, tremors, convulsions, and ultimately respiratory depression and coma [3-6]. Long term exposure to organophosphate insecticides is also associated with central and peripheral neurotoxicity in the form of cognitive and memory impairments, ataxia, delayed peripheral neuropathy [7-9]. Organophosphates have also been incriminated in the development of neurodegenerative diseases like Parkinson’s disease [10-12]. In this context, individuals with inefficient catalytic activity of paraoxonase 1, an enzyme important for the detoxification of organophosphates are more prone to develop Parkinson’s disease upon exposure to these insecticides [12-14].

Ethamsylate Protects Against the Carbon Tetrachloride-Induced Liver Damage in Rats

Ethamsylate (diethylammonium 1, 4 -dihydroxy-3benzenesulphonate) is a synthetic haemostatic drug used to reduce bleeding in conditions such as menorrhagia [1] and after transurethral resection for benign enlargement of the prostate [2]. The agent has also been used to reduce the risk of cerebral haemorrhage in premature infants, but controversial data have been reported [3,4]. In healthy humans receiving aspirin, ethamsylate decreased the bleeding time and blood loss [5]. Ethamsylate appears to ensure haemostasis by increasing plateletleukocyte aggregates [6]. The drug also exhibited other important pharmacological actions, scavenging hydroxyl radicals [7], inhibiting prostaglandin synthesis [8], decreasing inflammation [9] and decreasing vascular peritoneal permeabilization due to arachidonate [7].

Modulation of Neurobehavioral and Biochemical Alterations Induced by Aluminum Chloride with Cannabis sativa Extract

Cannabis sativa preparations in the form of marijuana (the dried flowering tops and leaves) and hashish (the dried resin and compressed flowers) from the female plant Cannabis sativa is the most widely used illicit drugs worldwide. In humans, cannabis is associated with a spectrum of central nervous system effects. These include euphoria, relaxation and perceptual alterations, which are mediated by Δ9-tetrahydrocannabinol (Δ9-THC) the primary psychoactive constituent of cannabis. Other cannabinoids include cannabinol, cannabidiol, cannabigerol, cannabichromene, and cannabidivarin. Cannabinoid CB1 receptors have been cloned and identified in high concentration in several brain regions eg., hippocampus, basal ganglia, cerebellum and cerebral cortex.