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Introduction: Sodium fluoride/potassium oxalate (NaF/KOx) tubes has been regarded as the gold-standard tubes for glucose analysis. Even though their ineffectiveness in immediately inhibiting glycolysis has been reported in several studies especially in the first 1-4h, they are still used in our clinical biochemistry laboratory for glucose measurement. However, in its absence, only serum separator tubes are employed for glucose measurement. We aim to determine whether serum separator tubes (SSTs) can replace NaF/KOx tubes for laboratory measurement of blood glucose and to assess the stability of glucose concentrations for 3 days period. Methods and findings: NaF/KOx tube type was the reference method while SSTs type was the candidate method for glucose measurement. A total of 50 paired samples collected separately in NaF/KOx tubes and SSTs from healthy adult participants in the Gambia Adults Reference Intervals Study (GARIS) project were used as the project sample size. Following blood collection and separation, the glucose concentration was measured within 2 h, and at 24h, 42h and 72h time-points. Our data analysis showed no significant difference in the mean glucose concentrations between the reference tube and candidate tube types (Mean difference = 0.06 mmol/L; P = 0.38) recorded in the different timepoints. Using growth trajectory and mixed effects model, the study data further showed no significant change in the glucose concentrations (p = 0.25) for three days period. Conclusions: The study confirms that SSTs can produce similar glucose results when employed in the absence of NaF/KOx tubes. Besides, the glucose concentrations were stable in both tubes for three days when the samples were separated within 2 h and refrigerated in 2-8°C.
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BACKGROUND: The aim of this study was to determine the prevalence of invasive bacterial infections and their antimicrobial resistance patterns in sickle cell disease (SCD) patients admitted at the Medical Research Council the Gambia (MRCG) Ward in the era of PCV and Hib vaccination in the Gambia. METHODS AND RESULTS: This study was conducted in the clinical laboratory department of MRCG. We retrospectively generated haematological, and blood culture data from our electronic medical records from 2015 to 2022 of SCD patients admitted to MRCG Ward. Of 380 SCD patients, blood culture was requested only for 159. Of the 159 admitted SCD, 11 patients had qualified positive blood cultures. Five different types of bacterial pathogens were isolated from these positive blood cultures: 4 Staphylococcus aureus, 3 Streptococcus pneumoniae, 2 Salmonella species, 1 Enterococcus species, and 1 Shigella boydii. No episode of bacteremia caused by Haemophilus influenzae type b was identified. The molecular serotyping of the Streptococcus pneumoniae isolates revealed non-vaccine serotypes 10 A, 12 F and 12 F. Penicillin resistance was recorded in two of the three Streptococcus pneumoniae. The Staphylococcus aureus isolates were penicillin resistant but cefoxitin sensitive, hence no methicillin (oxacillin) resistant Staphylococcus aureus was reported. Generally, the isolated pathogens were all sensitive to chloramphenicol, and vancomycin. The haematological indices were not significantly varied between SCD patients with and without microbiologically confirmed bacterial infection. CONCLUSION: Streptococcus pneumoniae and Staphylococcus aureus were the most common cause of bacteremia in these admitted SCD patients. The presence of non-typhoidal Salmonella and Shigella infection coupled with penicillin resistance should be considered during penicillin prophylaxis and empirical treatment regimens for SCD patients and future SCD management policies in the Gambia. The haematological parameters may not be reliable biomarkers in differentiating bacterial from non-bacterial infections in SCD patients.
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Anemia de Células Falciformes , Antiinfecciosos , Bacteriemia , Staphylococcus aureus Resistente a Meticilina , Infecciones Estafilocócicas , Humanos , Prevalencia , Gambia/epidemiología , Estudios Retrospectivos , Anemia de Células Falciformes/complicaciones , PenicilinasRESUMEN
The clinical efficacy of haloperidol in the treatment of psychosis has been limited by its tendency to cause parkinsonian-like motor disturbances such as bradykinesia, muscle rigidity and postural instability. Oxidative stress-evoked neuroinflammation has been implicated as the key neuropathological mechanism by which haloperidol induces loss of dopaminergic neurons and motor dysfunctions. This study was therefore designed to evaluate the effect of Jobelyn® (JB), an antioxidant supplement, on haloperidol-induced motor dysfunctions and underlying molecular mechanisms in male Swiss mice. The animals were distributed into 5 groups (n = 8), and treated orally with distilled water (control), haloperidol (1 mg/kg) alone or in combination with each dose of JB (10, 20 and 40 mg/kg), daily for 14 days. Thereafter, changes in motor functions were evaluated on day 14. Brain biomarkers of oxidative stress, proinflammatory cytokines (tumor necrosis factor-alpha and interleukin-6), cAMP response-element binding protein (CREB), mitogen-activated protein kinase (MAPK) and histomorphological changes were also investigated. Haloperidol induces postural instability, catalepsy and impaired locomotor activity, which were ameliorated by JB. Jobelyn® attenuated haloperidol-induced elevated brain levels of MDA, nitrite, proinflammatory cytokines and also boosted neuronal antioxidant profiles (GSH and catalase) of mice. It also restored the deregulated brain activities of CREB and MAPK, and reduced the histomorphological distortions as well as loss of viable neuronal cells in the striatum and prefrontal cortex of haloperidol-treated mice. These findings suggest possible benefits of JB as adjunctive remedy in mitigating parkinsonian-like adverse effects of haloperidol through modulation of CREB/MAPK activities and oxidative/inflammatory pathways.
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Antioxidantes , Haloperidol , Animales , Masculino , Ratones , Antioxidantes/metabolismo , Antioxidantes/farmacología , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Citocinas , Haloperidol/farmacología , Proteínas Quinasas Activadas por MitógenosRESUMEN
Epidemiological studies have implicated copper as one of the key environmental risk factors for the pathogenesis of depression. However, the precise mechanism by which copper contribute to the genesis of depression particularly the involvement of oxidative stress-driven neuroinflammation is yet to be fully investigated. Thus, this study was designed to evaluate the effects of copper sulfate (CuSO4) on depression-like behaviors and the role of oxidative stress and pro-inflammatory cytokines in mice. Forty male Swiss mice were distributed into control and three test groups (n = 10), and were treated orally with distilled water (10 mL/kg) or CuSO4 (25, 50 and 100 mg/kg) daily for 28 days. Afterwards, the tail suspension, forced swim, and sucrose splash tests were used for the detection of depression-like effects. The animals were then euthanized and the brains were processed for the estimation of biomarkers of oxidative stress and pro-inflammatory cytokines (tumor necrosis factor-alpha and interleukin-6). The histomorphological features and neuronal viability of the prefrontal cortex, hippocampus and striatum were also determined. Mice exposed to CuSO4 displayed depression-like features when compared with controls. The brain concentrations of malondialdehyde, nitrite and pro-inflammatory cytokines were elevated in CuSO4-treated mice. Mice exposed to CuSO4 also had reduced brain antioxidant status (glutathione, glutathione-s-transferase, total thiols, superoxide-dismutase and catalase), as well as altered histomorphological features, and decreased population of viable neuronal cells. These findings suggest that CuSO4 increases oxidative stress and pro-inflammatory cytokines to elicit depression-like effects in mice.
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Cobre , Citocinas , Masculino , Animales , Ratones , Citocinas/metabolismo , Sulfato de Cobre/farmacología , Depresión/inducido químicamente , Sulfatos/farmacología , Estrés Oxidativo , Glutatión/metabolismo , HipocampoRESUMEN
Antimicrobial resistance is a global health threat and efforts to mitigate it is warranted, thus the need for local antibiograms to improve stewardship. This study highlights the process that was used to develop an antibiogram to monitor resistance at a secondary-level health facility to aid empirical clinical decision making in a sub-Saharan African county. This retrospective cross-sectional descriptive study used 3 years of cumulative data from January 2016 to December 2018. Phenotypic data was manually imputed into WHONET and the cumulative antibiogram constructed using standardized methodologies according to CLSI M39-A4 guidelines. Pathogens were identified by standard manual microbiological methods and antimicrobial susceptibility testing was performed using Kirby-Bauer disc diffusion method according to CLSI M100 guidelines. A total of 14,776 non-duplicate samples were processed of which 1163 (7.9%) were positive for clinically significant pathogens. Among the 1163 pathogens, E. coli (n = 315) S. aureus (n = 232), and K. pneumoniae (n = 96) were the leading cause of disease. Overall, the susceptibility for E. coli and K. pneumoniae from all samples were: trimethoprim-sulfamethoxazole (17% and 28%), tetracycline (26% and 33%), gentamicin (72% and 46%), chloramphenicol (76 and 60%), and ciprofloxacin (69% and 59%), and amoxicillin/clavulanic (77% and 54%) respectively. Extended spectrum beta-lactamase (ESBL) resistance was present in 23% (71/315) vs. 35% (34/96) respectively. S. aureus susceptibility for methicillin was 99%. This antibiogram has shown that improvement in combination therapy is warranted in The Gambia.
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ETHNOPHARMACOLOGICAL RELEVANCE: The seed of the African walnut, Plukenetia conophora Mull.-Arg is well-known for its nutritional and medicinal values. The seed oil is widely used in massages to relieve pain, as nerve tonic and to enhance sexual performance. OBJECTIVE: The study aimed at investigating the chemical profile, antinociceptive and anti-inflammatory activities of P. conophora oil (PCO). METHODS: Seed oil of P. conophora was characterized using Gas-Liquid Chromatographic method (GC-MS) and oral acute toxicity evaluated at 2000 mg/kg. Antinociceptive effects were evaluated in hot plate, acetic acid and formalin-induced paw licking tests. The anti-inflammatory effects were investigated in egg albumin and carrageenan-, formalin and complete Freund adjuvant (CFA)-induced paw oedema models. The levels of pro-inflammatory cytokines in the fluid exudates were also evaluated in carrageenan air pouch model. RESULTS: PCO exhibited high content of alpha linolenic acid (ALA). No toxicity was observed at 2000 mg/kg of PCO. PCO (50-200 mg/kg) demonstrated significant anti-nociceptive activity in pain models. PCO exhibited anti-inflammatory activity against oedema formation by phlogistic agents. The increased inflammatory oedema and oxidative stress in CFA-treated rats were also attenuated by PCO. The PCO (100 and 200 mg/kg) significantly reduced the levels of TNF-α (59.3% and 85.2%) and IL-6 (27.5% and 72.5%) in carrageenan-induced air pouch model. CONCLUSION: The results of this study suggest that ALA-rich seed oil of Plukenetia conophora demonstrated anti-nociceptive and anti-inflammatory activities via inhibition of pro-inflammatory cytokines and oxidative stress, lending supportive evidences for its use in painful inflammatory conditions.
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Analgésicos , Extractos Vegetales , Ratas , Animales , Carragenina , Analgésicos/farmacología , Analgésicos/uso terapéutico , Analgésicos/química , Extractos Vegetales/farmacología , Roedores , Antiinflamatorios/efectos adversos , Dolor/inducido químicamente , Dolor/tratamiento farmacológico , Citocinas/uso terapéutico , Formaldehído , Aceites de Plantas/efectos adversos , Semillas , Edema/inducido químicamente , Edema/tratamiento farmacológicoRESUMEN
Alcohol-induced aggression and related violence is a serious and common social problem globally. Alcohol use is increasingly found in the form of alcoholic herbal mixtures (AHM) with indiscriminate and unregulated alcohol content. This study investigated the effects of AHM on aggressive-like, neurocognitive impairment and brain biochemical alteration in mice. Thirty-two male resident mice were paired housed with female mice for 21 days in four groups (n = 8). Resident mice were treated orally with normal saline, AHM, ethanol and AHM + ethanol daily for 14 days. Aggressive-like behaviour was scored based on the latency and frequency of attacks by the resident mouse on the intruder. Neurocognitive impairment was determined using the Y-maze test (YMT) and novel object recognition test (NORT). Acetylcholinesterase, glutamic acid decarboxylase (GAD), pro-inflammatory and oxidative stress parameters were determined in the prefrontal cortex (PFC). Neuronal morphology, cytochrome c (Cyt-c) and nuclear factor-kappa B (NF-ĸB) expressions were determined. AHM and in combination with ethanol showed an increased index of aggression typified by frequency of attack and reduced latency to attack when compared to normal saline-treated animals. Co-administration of AHM and ethanol significantly reduced cognitive correct alternation (%) and discrimination index in the YMT and NORT, respectively. AHM and ethanol increased acetylcholinesterase, Pro-inflammatory cytokines and oxidative stress parameters while they reduced GAD. There were significantly reduced neuronal counts and increased expression of Cyt-c and NF-ĸB, respectively Alcoholic herbal mixture increased aggressiveness and caused neurocognitive impairment via increased oxido-inflammatory stress in the prefrontal cortex.
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Acetilcolinesterasa , FN-kappa B , Ratones , Masculino , Femenino , Animales , Acetilcolinesterasa/metabolismo , FN-kappa B/metabolismo , Enfermedades Neuroinflamatorias , Solución Salina/metabolismo , Solución Salina/farmacología , Etanol/toxicidad , Corteza Prefrontal/metabolismo , Agresión , ApoptosisRESUMEN
The leaves of Clerodendrum polycephalum Baker (Labiatae) are used as a dietary legume supplement and applied ethnomedicinally for the management of epilepsy, convulsion, and spasms. This study is aimed at evaluating the effects of Clerodendrum polycephalum (CP) leaf extract on chemical-induced seizures in mice and the possible mechanisms of action. Swiss albino mice were pretreated with CP (50, 100, or 500 mg/kg, p.o.) prior to intraperitoneal injection of picrotoxin (PTX) or pentylenetetrazole (PTZ). However, the most effective dose was used to elucidate the role of GABAergic and nitric oxide-cyclic guanosine monophosphate (NO-cGMP) signaling mechanisms in mice brains. Accordingly, we evaluated the preventive and reversal effects of CP on kainic acid (KA)-induced temporal lobe epilepsy (TLE), oxidative stress, and neuroinflammatory in mice. The pretreatment of mice with CP delayed the latencies to PTX and PTZ-induced seizures and decrement in the period of tonic-clonic attacks. Interestingly, CP (100 mg/kg) completely prevented PTZ-induced tonic-clonic seizures. Contrastingly, flumazenil (benzodiazepine receptor antagonist), NG -nitro-L-Arginine (L-NNA) (10 mg/kg., neuronal nitric oxide synthase inhibitor), and methylene blue (MB) (2 mg/kg, a soluble guanylyl cyclase inhibitor) but not L-arginine (150 mg/kg., nitric oxide precursor) reversed CP-induced anticonvulsant-like effect in PTZ model. Furthermore, KA-elicited TLE was prevented by CP treatment. CP also attenuated KA-induced oxidative stress, cyooxygenase-2 (COX-2), and nuclear factor kappa-B (NF-κB) elevated expressions in the hippocampus. The study revealed that the ethanolic leaf extract of CP produced anticonvulsant actions through enhancement of antioxidant defense, GABAergic, and NO-cGMP signaling pathways as well as attenuation of inflammatory processes. PRACTICAL APPLICATIONS: The leaves of Clerodendrum polycephalum Baker (Labiatae) are used as a dietary legume supplement and applied ethnomedicinally for the management of epilepsy, convulsion, and spasms. For this reason, we believe that supplementation of the Clerodendrum polycephalum leaf extract would prevent epileptic-related disorders in mice induced with epileptic conditions using kainic acid and other behavioral phenotypic models. Here, our findings clearly revealed that Clerodendrum polycephalum leaf extract protects against conditions of epileptic-related disorders and thus might be relevant as a dietary supplement in the prevention or delay of the onset of seizures and epileptic behavior.
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Clerodendrum , Lamiaceae , Animales , Anticonvulsivantes/farmacología , Antioxidantes/uso terapéutico , Arginina , Clerodendrum/metabolismo , Ciclooxigenasa 2/metabolismo , Flumazenil , Guanosina Monofosfato , Ácido Kaínico , Azul de Metileno , Ratones , FN-kappa B/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa de Tipo I/metabolismo , Pentilenotetrazol , Picrotoxina , Extractos Vegetales/farmacología , Receptores de GABA-A/uso terapéutico , Convulsiones/inducido químicamente , Convulsiones/tratamiento farmacológico , Guanilil Ciclasa Soluble/metabolismo , Espasmo/tratamiento farmacológicoRESUMEN
Development of neuropsychiatric disorder is associated with stress-related increase in pro-inflammatory cytokines. Chrysophyllum albidum fruit is an edible tropical fruit containing vitamins and phenolic compounds, well known for their anti-inflammatory and antioxidant activities. This study was designed to investigate the neuroprotective effect of C. albidum fruit extract (CAFE) on stress and lipopolysaccharide (LPS)-induced behavioral and neurochemical impairments in mice. Male Swiss mice were divided into 6 groups (n = 6). Groups 1-3 were orally treated daily for 14 days with normal saline (0.1 mL/10 g), CAFE (100 mg/kg) and Ferulic acid (FA, 10 mg/kg), and left in home cage as controls. Groups 4-6 were treated similarly but subjected to repeated social defeat (RSD) stress using the resident-intruder model from days 1-14. The RSD-animals were injected with LPS (125 µg/kg, i.p) 60 min after each RSD session from days 8-14. Neurobehavioral functions: locomotor, cognitive and anxiety-like behaviors were assessed 24 h after the last treatment. Pro-inflammatory cytokines (IL-1ß, IL-6 and TNF-α), dopamine, acetylcholinesterase, glutamic acid decarboxylase (GAD), malondialdehyde, nitrites, and reduced glutathione (GSH) were determined in brain tissue. CAFE significantly attenuated RSD and LPS-induced hypolocomotion, cognitive impairment and anxiety-like behavior when compared to the control. Treatment with CAFE also significantly reversed the negative effects of RSD and LPS on pro-inflammatory cytokines, dopamine, acetylcholinesterase, GAD, and oxidative-nitrosative stress levels. The findings clearly indicated that Chrysophyllum albidum fruit demonstrated neuroprotective effects and can play a key role in mitigating against chronic stress and inflammation linked to neuropsychiatric disorders.
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Fármacos Neuroprotectores , Sapotaceae , Animales , Ratones , Masculino , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Lipopolisacáridos/farmacología , Acetilcolinesterasa , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Derrota Social , Frutas/química , Frutas/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Interleucina-6 , Nitritos/análisis , Nitritos/farmacología , Dopamina , Glutamato Descarboxilasa/análisis , Glutamato Descarboxilasa/farmacología , Solución Salina/farmacología , Sapotaceae/química , Sapotaceae/metabolismo , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Glutatión/farmacología , Citocinas , Malondialdehído/farmacología , Vitaminas , Estrés OxidativoRESUMEN
BACKGROUND: Current evidences have implicated copper in amyloid aggregation that trigger the downstream oxidative stress-mediated neuroinflammation that characterized memory deterioration in patients with Alzheimer's disease (AD). Thus, this study was designed to evaluate the effect of D-Ribose-L-Cysteine (DRLC), a potent antioxidant agent, on copper sulfate (CuSO4)-induced memory deterioration and the biochemical mechanisms underpinning its action in mice. METHODS: Male Swiss mice were randomly distributed into 5 groups (n = 10/group). Mice in group 1 were given distilled water (control), group 2 CuSO4 (100 mg/kg) while groups 3-5 were pretreated with CuSO4 (100 mg/kg) 30 min before administration of DRLC (10, 25 and 50 mg/kg). Treatments were given through oral gavage, daily for 28 days. Memory function was evaluated on day 28 using Y-maze test. The isolated liver and brain tissues were then processed for oxidative stress biomarkers, and proinflammatory cytokines [tumor necrosis factor- α (TNF-α) and interleukin-6)] assays. Brian acetylcholinesterase (AChE) and liver enzymes [aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities were also determined. RESULTS: DRLC reversed memory impairment and dysregulated levels of malondialdehyde, glutathione, nitrite and glutathione S-transferase in the liver and brain tissues of mice pretreated with CuSO4. The increased proinflammatory cytokines concentrations in the liver and brain tissues of mice pretreated with CuSO4 were reduced by DRLC. The elevated brain AChE and liver enzymes activities induced by CuSO4 were also reduced by DRLC. CONCLUSION: Taken together, these findings suggest that DRLC attenuates CuSO4-induced memory dysfunctions in mice through enhancement of antioxidative pathway, inhibition of pro-inflammatory cytokines and augmentation of liver function.
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Sulfato de Cobre , Citocinas , Acetilcolinesterasa/metabolismo , Animales , Antioxidantes/metabolismo , Antioxidantes/farmacología , Sulfato de Cobre/metabolismo , Sulfato de Cobre/farmacología , Cisteína/análogos & derivados , Citocinas/metabolismo , Hígado/metabolismo , Masculino , Trastornos de la Memoria/inducido químicamente , Trastornos de la Memoria/tratamiento farmacológico , Ratones , Estrés Oxidativo , Ribosa/metabolismo , Ribosa/farmacología , TiazolidinasRESUMEN
Jobelyn® (JB), a dietary supplement, derived from polyphenol-rich leaf sheath of Sorghum bicolor, has been reported to attenuate sensorimotor deficits and oxidative stress evoked by complete Freund-adjuvant in mice. This present study evaluated its effects on the life span, motor function and changes in oxidative stress parameters as well as acetylcholinesterase activity in Drosophila melanogaster exposed to lipopolysaccharide (LPS). The flies (50 per vial), in 5 replicates were fed with LPS (250 µg/kg diet) alone or in combination with JB (0.25-1.0 mg/kg diet) daily for 7 days. The mortality rate and motor function were evaluated on day 7. The flies were afterwards processed for determination of oxidative stress parameters and acetylcholinesterase activity. The effects of JB (0.25-1.0 mg/g diet) on the longevity of Drosophila was also investigated wherein the flies were monitored daily for mortality throughout their lifespan. The flies exposed to LPS (250 µg/kg diet) had reduced life span and elevated oxidative stress when compared with control. However, JB (0.25 and 1.0 mg/kg diet) improved the motor function and also reduced the mortality rate of the flies exposed to LPS. It also restored the cellular antioxidant status and reduced acetylcholinesterase activity, accumulation of hydrogen peroxide as well as nitric oxide in Drosophila fed with LPS. JB also extended the longevity of the flies relative to control. The findings that JB improves motor function and extended the lifespan of Drosophila flies by boosting the antioxidant status and cholinergic function, suggest it might be helpful in delaying the onset of neuropsychiatric illnesses associated with the aging processes.
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Antioxidantes , Longevidad , Acetilcolinesterasa , Animales , Antioxidantes/farmacología , Drosophila melanogaster , Adyuvante de Freund/farmacología , Lipopolisacáridos/farmacología , RatonesRESUMEN
A substantial number of epileptic patients are resistant to the current medication thus necessitating the search for alternative therapies for intractable forms of the disease. Previous studies demonstrated the acute anticonvulsant properties of the methanol extract of the stem bark of Psychotria camptopus (MEPC) in rats. This study investigated the effects of MEPC on pentylenetetrazole-kindled Wistar rats. Kindling was induced by intraperitoneal injection of pentylenetetrazole (37.5 mg/kg) on every alternate day, 1 h after each daily oral pretreatment of rats (8 ≤ n ≤ 10) with MEPC (40, 80 and 120 mg/kg), vehicle or diazepam (3 mg/kg) for 43 days. The kindling development was monitored based on seizure episodes and severity. Rats' brains were collected on day 43 for the determination of oxidative stress parameters. The histomorphological features and neuronal cell viability of the prefrontal cortex (PFC) and hippocampus were also assessed using H&E and Cresyl violet stains. Chronic administration of pentylenetetrazole time-dependently decreased the latency to myoclonic and generalized seizures, and increased seizure scores and the number of kindled rats. MEPC and diazepam significantly increased the latencies to myoclonic jerks and generalized tonic-clonic seizures. These substances also reduced seizure score and the number of rats with PTZ-kindling. MEPC improved glutathione status and decreased lipid peroxidation in the brains of kindled rats. MEPC also exhibited neuroprotection against pentylenetetrazole-induced hippocampal and PFC neuronal damages. These results suggest that P. camptopus has antiepileptogenic activity, which might be related to the augmentation of antioxidant and neuroprotective defense mechanisms, and further confirm its usefulness in the management of epilepsy.
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Excitación Neurológica , Fármacos Neuroprotectores , Psychotria , Rubiaceae , Animales , Anticonvulsivantes/farmacología , Anticonvulsivantes/uso terapéutico , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Humanos , Masculino , Metanol/farmacología , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Pentilenotetrazol/farmacología , Corteza de la Planta , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Ratas , Ratas WistarRESUMEN
This study investigated the effect of high doses of monosodium glutamate (MSG), a known food additive on hepatic, memory and locomotor functions in mice, and the ameliorative potentials of Jobelyn® (JB), a unique dietary supplement. Twenty four male Swiss mice divided into 4 groups (n = 6) were given MSG (2, 4 and 8 g/kg) or normal saline (10 mL/kg) orally for 14 days. In the intervention study, another set of 30 male Swiss mice distributed into 5 groups (n = 6) received normal saline, MSG (8 g/kg) alone or in combination with JB (5, 10 and 20 mg/kg) orally, for 14 days. Memory and locomotor functions as well as brain oxido-nitrergic stress biomarkers were then assessed in both studies. The hepatic oxido-nitrergic stress biomarkers, liver enzymes functions and histomorphology of the liver were also assessed. MSG (2, 4 and 8 g/kg) produced memory dysfunction, hyperlocomotion, increased malondialdehyde and nitrite levels accompanied by decreased antioxidant status in the brain and hepatic tissues. MSG-treated mice had increased hepatic enzyme activities (alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase) and distorted cyto-architectural integrity of the liver. These findings further suggest that MSG compromised hepatic functioning, which might also contribute to its neurotoxicity. However, JB (5, 10 and 20 mg/kg, p.o) attenuated the memory deficit, hyperlocomotion, increased oxido-nitrergic stress responses in the brain and hepatic tissues induced by MSG (8 g/kg, p.o). JB also normalized hepatic enzymes activities and histomorphological changes in MSG-treated mice. Taken together, JB mitigated MSG-induced toxicity through mechanisms relating to enhancement of cellular antioxidant-machineries and normalization of hepatic enzymatic functions.
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Mounting evidences have shown that nicotinamide adenine dinucleotide phosphate oxidase-2 (Nox-2) pathway modifies glutamic-acid decarboxylase-67 (GAD67) (GABAergic enzyme) and cholinergic systems via oxidative-nitrergic mechanisms in schizophrenia pathology. Rutin, a neuroactive antioxidant compound, with proven neuroprotective property has been shown to reduce schizophrenic-like behavior in mice. This study sought to investigate the mechanisms of action of the psychopharmacological activity of rutin in the preventive and reversal effects of ketamine-induced schizophrenic-like behavior, oxidative-nitrergic stress, cholinergic and GABAergic derangements in mice. In the preventive treatment, male mice were given rutin (0.1, 0.2 and 0.4 mg/kg) or risperidone (0.5 mg/kg) orally for 14 days prior to ketamine (20 mg/kg, i.p.) treatment from the 8 to 14th day. However, in the reversal treatment, ketamine was given for 14 days prior to rutin and risperidone. Behavioral (open-field, social-interaction and Y-maze tests), biochemical (oxidative/nitrergic stress markers, acetylcholinesterase activity), immunohistochemical (GAD67, Nox-2) and neuronal cell deaths in the striatum, prefrontal cortex, and hippocampus were evaluated. Ketamine-induced behavioral impairments were prevented and reversed by rutin. Exposure of mice to ketamine increased malondialdehyde, nitrite contents, acetylcholinesterase activity, neuronal cell death and Nox-2 expressions in the striatum, prefrontal cortex and hippocampus. Conversely, these derangements were prevented and reversed by rutin. The decreased glutathione levels due to ketamine were marked increased by rutin. Rutin only prevented ketamine-induced decrease in GAD67 expression in the striatal-hippocampal region. Altogether, the study showed that the prevention and reversal treatments of mice with rutin attenuated ketamine-induced schizophrenic-like behaviors via reduction of Nox-2 expression, oxidative/nitrergic stresses, acetylcholinesterase activity, and increased GAD67 enzyme.
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Colinérgicos/metabolismo , Glutamato Descarboxilasa/metabolismo , NADPH Oxidasa 2/metabolismo , Estrés Oxidativo , Rutina/uso terapéutico , Esquizofrenia/genética , Esquizofrenia/prevención & control , Acetilcolinesterasa/metabolismo , Animales , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Encéfalo/patología , Regulación hacia Abajo/efectos de los fármacos , Glutatión/metabolismo , Ketamina , Locomoción/efectos de los fármacos , Masculino , Malondialdehído/metabolismo , Trastornos de la Memoria/complicaciones , Trastornos de la Memoria/tratamiento farmacológico , Ratones , Nitritos/metabolismo , Estrés Oxidativo/efectos de los fármacos , Rutina/farmacología , Esquizofrenia/inducido químicamente , Esquizofrenia/tratamiento farmacológico , Interacción Social , Memoria Espacial/efectos de los fármacos , Regulación hacia Arriba/efectos de los fármacosRESUMEN
Methyl jasmonate (MJ) is a derivative of the jasmonate family which is found in most tropical regions of the world and present in many fruits and vegetables such as grapevines, tomato, rice, and sugarcane. MJ is a cyclopentanone phytohormone that plays a vital role in defense against stress and pathogens in plants. This has led to its isolation from plants for studies in animals. Many of these studies have been carried out to evaluate its therapeutic effects on behavioral and neurochemical functions. It has however been proposed to have beneficial potential over a wide range of neurological disorders. Hence, this review aims to provide an overview of the neuroprotective properties of MJ and its probable mechanisms of ameliorating neurological disorders. The information used for this review was sourced from research articles and scientific databases using 'methyl jasmonate', 'behavior', 'neuroprotection', 'neurodegenerative diseases', and 'mechanisms' as search words. The review highlights its influences on behavioral patterns of anxiety, aggression, depression, memory, psychotic, and stress. The molecular mechanisms such as modulation of the antioxidant defense, inflammatory biomarkers, neurotransmitter regulation, and neuronal regeneration, underlying its actions in managing neurodegenerative diseases like Alzheimer's and Parkinson's diseases are also discussed. This review, therefore, provides a detailed evaluation of methyl jasmonate as a potential neuroprotective compound with the ability to modify behavioral and molecular biomarkers underlying neurological disorders. Hence, MJ could be modeled as a guided treatment for the management of brain diseases.
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Oxidative and inflammatory signaling pathways have been identified as important targets for mitigating hypoxic stress-induced neurological complications. Thus, the effects of naringenin, a potent antioxidant, anti-inflammatory and neuroprotective bioflavonoid on hypoxic stress-induced depressive-like and anxiety-related behaviors in mice, and the underlying molecular mechanisms were evaluated in this study. Thirty-five male Swiss mice were distributed into 5 groups (nâ¯=â¯7). Mice in group I (non-stress control) and group 2 (stress-control) both had vehicle (5 % DMSO), while groups 3-5 received naringenin (10, 25 and 50â¯mg/kg), intraperitonally. Thirty minutes later, mice in groups 2-5 were subjected to 15â¯min hypoxic stress, daily for 14 days. Locomotor activity, anxiety and depression were evaluated on day 15. The mice brains were processed for malondialdehyde, glutathione, superoxide-dismutase (SOD), catalase, tumor necrosis factor-alpha (TNF-α) and interleukin-1ß assays. The serum corticosterone concentration and expressions of the brain immunopositive cells of inducible nitric oxide synthase (iNOS), nuclear factor kappa-B (NF-kB) and brain derived neurotrophic factor (BDNF) as well as histomorphological changes of the amygdala were also determined. Naringenin (25-50â¯mg/kg) ameliorated the hypolocomotion, depressive- and anxiety-like behaviors in hypoxic mice. The increased brain contents of malondialdehyde, TNF-α, interleukin-1ß, and decreased antioxidant (glutathione and SOD) status were attenuated by naringenin. Naringenin (10â¯mg/kg) increases BDNF expression but did not significantly (pâ¯<â¯0.05) alter corticosterone and catalase contents. The increased expressions of iNOS and NF-kB as well as loss of amygdala neuronal cells were reduced by naringenin (10â¯mg/kg). Overall, these findings suggest that naringenin improves depressive- and anxiety-like behaviors in mice exposed to hypoxic stress by modulating oxido-inflammatory insults and NF-kB/BDNF expressions.
Asunto(s)
Ansiedad/tratamiento farmacológico , Depresión/tratamiento farmacológico , Flavanonas/uso terapéutico , Hipoxia/metabolismo , Inflamación/metabolismo , Estrés Oxidativo/efectos de los fármacos , Animales , Ansiolíticos/farmacología , Ansiolíticos/uso terapéutico , Antidepresivos/farmacología , Antidepresivos/uso terapéutico , Ansiedad/metabolismo , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Catalasa/metabolismo , Corticosterona/sangre , Depresión/metabolismo , Flavanonas/farmacología , Glutatión/metabolismo , Interleucina-1beta/metabolismo , Masculino , Malondialdehído/metabolismo , Ratones , Actividad Motora/efectos de los fármacos , FN-kappa B/metabolismo , Óxido Nítrico Sintasa de Tipo II/metabolismo , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Objectives The contribution of anesthetic procedure to surgical stress and postoperative complications has been attributed to increased oxidative stress and release of inflammatory cytokines. Thus, the levels of oxidative stress biomarkers and inflammatory cytokines in patients with general anesthesia (GA) and spinal anesthesia (SA) that underwent open reduction and internal fixation (ORIF) in orthopedic surgery at Federal Teaching Hospital, Ido-Ekiti, Ekiti state, Nigeria were investigated. Methods Forty patients were randomly distributed into two groups (n = 20) namely GA and SA. Blood samples were collected before and after surgery for estimation of glucose, oxidative stress biomarkers (malondialdehyde [MDA], glutathione, catalase and nitrile) and inflammatory cytokines (tumor necrosis factor-α [TNF-α] and interleukin-6) levels. Results The post-operative blood glucose level was higher than the pre-operative value (p<0.5) in the two groups. There were significant (p<0.05) changes in MDA concentration and catalase activity in patients with GA in the post-operative stage relative to preoperative phase. There were no significant differences in glutathione, nitrite and interleukin-6 contents between the two groups. The patients with SA had higher levels of TNF-α in the post-operative stage. Conclusions These findings suggest that anesthesia has differential effects on oxidative stress and inflammatory cytokines in patients with ORIF orthopedic surgery.
RESUMEN
Adaptogens are substances that act nonspecifically to combat stress by regulating the key elements involved in stress-induced pathologies. D-Ribose-L-cysteine (DRLC), a potent glutathione (GSH) booster, has been recommended for relief of stress. Hence, we investigated its adaptogenic-like effect in mice subjugated to unpredictable chronic mild stress (UCMS). Thirty six male Swiss mice were assigned to 6 groups (n = 6): group 1 received saline (p.o, non-stress control), group 2 (stress-control) also had saline, groups 3 to 5 received DRLC (25, 50 and 100 mg/kg, p.o) whereas group 6 had ginseng (50 mg/kg, p.o). The animals in groups 2-6 were subjugated to UCMS 30 min later, daily for 21 days and afterwards, tested for memory and anxiety. Blood glucose, serum corticosterone concentrations and adrenal weight were determined. The brain tissues were processed for estimation of malondialdehyde (MDA), GSH, superoxide-dismutase (SOD), catalase, tumor necrosis factor-alpha (TNF-α), interleukin-6, acetyl-cholinesterase, and caspase-3 activities. The histomorphologic features and neuronal viability of the hippocampus, amygdala and prefrontal cortex were also determined. DRLC (25-100 mg/kg) reduces anxiety, memory deficit, adrenal gland enlargement, glucose, and corticosterone concentrations in UCMS-mice. The increased brain contents of MDA, TNF-α, interleukin-6, acetyl-cholinesterase and decreased antioxidant (GSH, SOD and catalase) status induced by UCMS were attenuated by DRLC. The DRLC increased caspase-3 activity and reduces histomorphological distortions of neuronal cells of the hippocampus, amygdala and prefrontal cortex of stressed-mice. These findings suggest that DRLC has adaptogenic-like effect which might be related to modulation of corticosterone-mediated oxido-inflammatory processes and altered caspase-3 activity.