Administration Of Monosodium Glutamate Research Articles

Phytochemical Evaluation of Lepidium meyenii, Trigonella foenum-graecum, Spirulina platensis, and Tribulus arabica, and Their Potential Effect on Monosodium Glutamate Induced Male Reproductive Dysfunction in Adult Wistar Rats.

Monosodium glutamate (MSG), a sodium salt derived from glutamic acid, is widely used in commercial food products to improve taste, quality, and preservation. However, its consumption may have detrimental effects on male reproductive function. Nevertheless, plant extracts, such as Lepidium meyenii (Maca), Trigonella foenum-graecum (Fenugreek), Spirulina platensis (Spirulina), and Tribulus arabica (Tribulus), may ameliorate these adverse effects. To this effect, the phytochemical properties of Lepidium meyenii, Trigonella foenum-graecum, Spirulina platensis, and Tribulus arabica were assessed, and their potential impact on MSG-induced impairment of reproductive parameters was examined. The phytochemical composition (steroids, terpenes, phenols, flavonoids) of the plants was profiled through spectrophotometry and the antioxidant activity was assessed using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging assay. Thirty-six male Wistar rats were divided into six groups at random: a control group receiving distilled water, and five experimental groups (MSG, Maca, Fenugreek, Spirulina, and Tribulus) receiving 900 mg/kg/day of MSG dissolved in water for 45 days. Subsequently, the animals in the experimental groups were administered 500 mg/kg/day of the respective plant extract via oral gavage for an additional 35 days, while the MSG group continued to receive water only. Following the treatment period, the animals were sacrificed, and their reproductive tract organs were collected, weighed, and subjected to further analysis. Phytochemical analysis revealed the presence of diverse bioactive elements in the plant extracts, including phenolic and flavonoid compounds. Exposure to MSG negatively impacted total and progressive sperm motility, which was ameliorated by Lepidium meyenii treatment. Sperm morphology showed no significant differences among groups. Treatment of the phytochemical agents diminished histomorphometric alternations of the testicular length, germinal epithelium height, and number of cells in seminiferous tubules, which were caused by the initial administration of MSG. Testosterone and LH levels were reduced in the MSG group but improved in extract-treated groups. The study suggests Lepidium meyenii as a potential remedy for reproductive dysfunction. However, further investigation into its mechanisms and human safety and efficacy is warranted.

Histological Assessment of Placental Development Following Maternal Administration of Monosodium Glutamate in Wistar Rats

Histological Assessment of Placental Development Following Maternal Administration of Monosodium Glutamate in Wistar Rats

The influence of monosodium glutamate on the development of oxidative-nitrosative stress in the large cerebral hemispheres of rats under the combination of a change in the “light-dark” cycle and a systemic inflammatory response

Today, the issue of the consequences of disrupting the normal “light-dark” cycle is becoming increasingly important, and the link between the development of a systemic inflammatory response (SIR) and circadian rhythm disorders has been confirmed. The effect of monosodium glutamate on the human body is being actively studied. The aim of the work was to find out the influence of monosodium glutamate on the development of oxidative-nitrosative stress in the homogenate of the large cerebral hemispheres of rats with a combination of acute desynchronosis (AD), SIR and administration of monosodium glutamate. Material and methods. The research was carried out on 72 white Wistar rats weighing 150–200 of different sexes, divided into 5 groups: control (n = 15), AD (n = 13), SIR (n = 15), a combination of SIR and AD (n = 14), a combination of SIR, AD, and glutamate (n = 15). To simulate AD, a normal “light-dark” cycle (12 hours of light, 12 hours of darkness) was formed for 3 weeks, and the next 3 days the “light-dark” phases were shifted back by 6 hours. SIR was reproduced by intraperitoneal injection of Salmonella typhi lipopolysaccharide in the first week at a dose of 0.4 μg/kg 3 times per week, the following seven weeks – once a week. Sodium glutamate was administered intragastrically for 20 days at a dose 30 mg/kg, dissolved in 0.5 ml of distilled water. In a 10 % homogenate of the large cerebral hemispheres, we determined the rate of superoxide anion radical (SAR) production, the content of products that react with thiobarbituric acid (TBA-reactants), their increase, activity of catalase, superoxide dismutase (SOD), ornithine decarboxylase (ODC), concentration of nitrites, peroxynitrites, total activity of NO-synthase (NOS), its constitutive (cNOS) and inducible (iNOS) isoforms. Results. In the group of SIR, AD and glutamate combination, compared to the control, the following was noted: an increase in the rate of basic production of SAR by 175.8 %, by the microsomal pathway by 20.0 %, by the mitochondrial pathway by 51.2 %, the concentration of TBA-reactants by 83.4 %, their increase – by 61.7 %, decrease in the activity of SOD by 57.1 %, catalase – by 38.1 %; an increase in peroxynitrite content by 116.7 %, ODC activity by 161.5 %, total NOS activity by 25.6 % and iNOS by 27.4 %, a decrease in cNOS activity by 15.0 % and nitrite concentration by 35.0 % in brain tissues. Conclusions. Sodium glutamate administration in combination with AD and SIR leads to increased oxidative-nitrosative stress, inhibition of antioxidant protection; contributes to the activation of the general activity of NO-synthase and iNOS, suppresses the activity of cNOS.

Multifaceted Impacts of Monosodium Glutamate on Testicular Health: Insights into Pyroptosis and Therapeutic Potential of Resveratrol.

Monosodium glutamate was considered one of the food additive and flavor enhancer in processed meat and soup that affects testicular tissues, the aim of this research to investigates the impact of monosodium glutamate (MSG) on testicular structure in rats and explores the potential protective effects of resveratrol. Four experimental groups involved in our study 10 rats of each.: the first group as control group; the second group (Resveratrol group: control rats received 20 mg/kg of resveratrol, via oral gavage); the third group (MSG group: rats received monosodium glutamate (MSG) with a dose 60 mg/kg body weight daily, via gastric tube, and the fourth group (MSG+ Resveratrol group). Serum level of testosterone, FSH, LH, were measured. Testicular tissues were prepared for measurement of oxidative stress markers, and gene expression of NLRP3, Caspase 3, and GSK-3β. Moreover, paraffin blocks contained testicular tissue used for histological and immunohistochemical examination. Additionally, seminal smear from epididymis were examined. MSG administration adversely affected testosterone production, hormonal levels, and sperm parameters, Histological examination revealed marked testicular degeneration, and oxidative stress assessments indicated elevated level of MDA a lipid peroxidation marker and decrease in SOD, CAT antioxidant enzymes. Moreover, MSG-induced apoptotic and pyroptotic markers and its gene expressions. Importantly. Administration of resveratrol reversed the detrimental effects of MSG, demonstrating its corrective influence on the hypothalamic-pituitary-gonadal axis disruption, improvement of sperm parameters, attenuation of oxidative stress, anti-apoptotic activity, and anti-pyroptotic effects. The expression of Ki-67 as a cell proliferation marker further supported the positive response to spermatogenesis dysfunction upon resveratrol treatment. This comprehensive exploration sheds light on the protective effect of resveratrol against MSG-induced testicular with exploration of its mechanistic role.

The potential protective effect of Camellia Sinensis in mitigating monosodium glutamate-induced neurotoxicity: biochemical and histological study in male albino rats

Monosodium glutamate (MSG) is the sodium compound derived from glutamic acid. Excessive daily ingestion of MSG leads to elevated amounts of glutamic acid in the bloodstream, which can be detrimental to brain structures. Camellia sinensis, often known as green tea (GT), is a rich source of essential hexogen antioxidants that are necessary for the body. Thirty-two adult male albino rats were divided into four groups (n = 8). Group 1 served as a control -ve group. Group 2 was given GT (1.5 ml/rat/day). Group 3 was given MSG (600 mg/kg/day). Group 4 was given MSG (600 mg/kg/day) and GT (1.5 ml/rat/day). All treatments were given orally for 28 days. MSG administration resulted in significant neurotoxicity in rats that was revealed by the significant reduction of serum concentration of glutathione peroxidase (GPx) and nitric oxide (NO), and the significant elevation of total antioxidant capacity (TAC) accompanied by the significant reduction of levels of serum monoamines (dopamine, serotonin, and norepinephrine) and histological changes in the hippocampus area CA1, dentate gyrus, and cerebellar cortex and positive immunohistochemical staining of glial fibrillary acidic proteins (GFAP) and calretinin. Administration of GT with MSG counteracted the MSG-mediated oxidative stress by significantly increasing serum concentrations of GPX and NO and significantly decreasing concentrations of TAC. Furthermore, GT significantly increased levels of serum monoamines (dopamine, serotonin, and norepinephrine). Moreover, it ameliorated the histological changes, GFAP, and calretinin immunostaining in brain tissues. It is envisaged that GT will serve as a viable protective choice for the inclusion of the neurotoxicity treatment procedure.

EFFECT OF LONG-TERM ADMINISTRATION OF MONOSODIUM GLUTAMATE ON BODY WEIGHT OF RATS AND SOME INDICES OF LIPID METABOLISM

EFFECT OF LONG-TERM ADMINISTRATION OF MONOSODIUM GLUTAMATE ON BODY WEIGHT OF RATS AND SOME INDICES OF LIPID METABOLISM

Central amygdala is related to the reduction of aggressive behavior by monosodium glutamate ingestion during the period of development in an ADHD model rat.

Monosodium glutamate (MSG), an umami substance, stimulates the gut-brain axis communication via gut umami receptors and the subsequent vagus nerves. However, the brain mechanism underlying the effect of MSG ingestion during the developmental period on aggression has not yet been clarified. We first tried to establish new experimental conditions to be more appropriate for detailed analysis of the brain, and then investigated the effects of MSG ingestion on aggressive behavior during the developmental stage of an ADHD rat model. Long-Evans, WKY/Izm, SHR/Izm, and SHR-SP/Ezo were individually housed from postnatal day 25 for 5 weeks. Post-weaning social isolation (PWSI) was given to escalate aggressive behavior. The resident-intruder test, that is conducted during the subjective night, was used for a detailed analysis of aggression, including the frequency, duration, and latency of anogenital sniffing, aggressive grooming, and attack behavior. Immunohistochemistry of c-Fos expression was conducted in all strains to predict potential aggression-related brain areas. Finally, the most aggressive strain, SHR/Izm, a known model of attention-deficit hyperactivity disorder (ADHD), was used to investigate the effect of MSG ingestion (60 mM solution) on aggression, followed by c-Fos immunostaining in aggression-related areas. Bilateral subdiaphragmatic vagotomy was performed to verify the importance of gut-brain interactions in the effect of MSG. The resident intruder test revealed that SHR/Izm rats were the most aggressive among the four strains for all aggression parameters tested. SHR/Izm rats also showed the highest number of c-Fos + cells in aggression-related brain areas, including the central amygdala (CeA). MSG ingestion significantly decreased the frequency and duration of aggressive grooming and attack behavior and increased the latency of attack behavior. Furthermore, MSG administration successfully increased c-Fos positive cell number in the intermediate nucleus of the solitary tract (iNTS), a terminal of the gastrointestinal sensory afferent fiber of the vagus nerve, and modulated c-Fos positive cells in the CeA. Interestingly, vagotomy diminished the MSG effects on aggression and c-Fos expression in the iNTS and CeA. MSG ingestion decreased PWSI-induced aggression in SHR/Izm, which was mediated by the vagus nerve related to the stimulation of iNTS and modulation of CeA activity.

Mitochondrial dysfunction of the inner membrane of hepatocytes in the development of glutamate-induced steatohepatosis and its correction

Elucidation of the mechanisms of the development of liver steatosis, which are at the heart of the pathogenesis of nonalcoholic fatty liver disease (NAFLD), will allow the introduction of new effective treatment methods into medical practice, as well as the development of new measures for the correction of this disease and accompanying pathologies. The purpose of the research is to establish the enzymatic activity of the complexes of the electron transport chain of the mitochondrial membrane of rat hepatocytes and to evaluate the corrective effect of the multiprobiotic “Symbiter acidophilic” concentrated or nanocrystalline cerium dioxide on the formation of steatohepatosis induced by neonatal sodium glutamate administration. The experiments were carried out on 50 white non-linear male rats; the direction included the study of the mechanisms of the development of steatohepatosis in 4-month-old rats, which were administered monosodium glutamate in the neonatal period, and the study of the functional state of the liver in rats after the neonatal administration of monosodium glutamate against the background of periodic administration of a multiprobiotic or nanocrystalline dioxide cerium. It was established that neonatal administration of monosodium glutamate causes metabolic changes in 4-month-old rats, manifested in the disproportionate accumulation of fat with the development of visceral obesity without hyperphagia, dyslipidemia, and steatohepatosis. In 4-month-old rats, after neonatal administration of sodium glutamate, the development of steatohepatosis was accompanied by mitochondrial dysfunction, which was manifested by changes in the lipid composition of the inner membrane of hepatocyte mitochondria with an increase in oxidized products and a change in the enzymatic activity of all complexes of the respiratory chain. In rats injected with monosodium glutamate in the neonatal period, periodic use of the multiprobiotic “Symbiter acidophilic” concentrated or nanocrystalline cerium dioxide significantly restored the functional state of the liver, reduced the manifestations of oxidative stress and prevented the development of steatohepatosis, which indicates the antioxidant effect of these drugs and the possibility of their use for prevention of steatohepatosis.

Hematological changes, oxidative stress assessment, and dysregulation of aquaporin-3 channel, prolactin, and oxytocin receptors in kidneys of lactating Wistar rats treated with monosodium glutamate.

High consumption of locally produced delicacies could expose nursing mothers to high monosodium glutamate (MSG) levels, frequently used as a necessary condiment in low-income countries. Thus, this study evaluated some novel preliminary changes in renal hormonal receptors, the aquaporin-3 channel, oxidative stress markers, and hematological indices induced by monosodium glutamate in lactating rats. Post-parturition, twenty-four (24) lactating Wistar rats were divided into four (4) groups of six rats each (n = 6). Oral administration of distilled water and MSG started three (3) days postpartum as follows: group 1: distilled water (1ml/kg BW), group 2: MSG (925mg/kg BW), group 3: MSG (1850mg/kg BW), and group 4: MSG (3700mg/kg BW). At the end of the experiment, which lasted fourteen (14) days, animals were sacrificed and samples of blood and tissues were obtained for biochemical analysis. MSG administration significantly (p < 0.05) increased ROS and MDA, with a significant (p < 0.05) decrease in kidney antioxidants. Serum creatinine, total, conjugated, and unconjugated bilirubin significantly (p < 0.05) increased with MSG administration. The prolactin receptor was significantly reduced (p < 0.05), while the oxytocin receptor and aquaporin-3 channel were significantly (p < 0.05) increased in the MSG-administered groups. There were significant (p < 0.05) changes in the hematological indices of the MSG-administered animals. Thus, the findings of this study suggest that high MSG consumption causes hematological alterations and may alter renal function via increased ROS production and dysregulation of the AQP-3 channel, prolactin, and oxytocin receptors in the kidneys of lactating Wistar rats.

Monosodium Glutamate Adversely Affects Serum Electrolytes and Antioxidant Status of Laying Hens

This research assessed the effect of varying inclusions of monosodium glutamate (MSG) on serum electrolytes and antioxidative enzymes of laying hens. A total of 300 Isa Brown point-of-lay pullets, aged 16 weeks, were evenly allocated to six distinct experimental lots, each containing different levels of MSG (0.00, 0.25, 0.50, 0.75, 1.00 and 1.25 g/kg). Throughout the study, the experimental hens were granted unrestricted freedom to diets, and clean water was consistently provided. In the twelfth week, five hens per replicate were chosen randomly after an overnight fast for blood collection through the wing veins. Standard procedures were employed to analyze serum electrolytes, including Na+ (sodium), K+ (potassium), and Cl- (chloride), together with antioxidant enzymes such as T-OAC (total antioxidant capacity), SOD (superoxide dismutase), and GSH-Px (glutathione peroxidase). Additionally, an assessment of the oxidative stress indicator malondialdehyde (MDA) was undertaken. The findings revealed that the addition of MSG at 1.00 and 1.25 g/kg in the feed significantly increased the serum Na+ concentration of the pullets, while the serum K+ level decreased significantly at the 1.25 g/kg MSG administration level, compared to the hens in the control group. In contrast, the blood Cl- level significantly decreased with MSG inclusion at the 0.50 g/kg level. Moreover, MSG inclusion levels at or above 0.75 g/kg led to an increase in MDA concentration, accompanied by a significant reduction in serum SOD, GSH-Px, and T-AOC levels. Thus, including MSG at levels exceeding 0.50 g/kg in the diet may potentially predispose laying hens to oxidative stress and other physiological imbalances.

Effect of Aqueous Leaves Extract of Datura alba ness (Thorn Apple) on Gonadotropic Hormones (FSH, LH) and Prolactin Following Administration of MSG and Clomiphene Citrate in Female Wistar Rats

Phytomedicine has become popular among and majority of women depends on herbal medicine when seeking healthcare. Several women opted for herbal medicine when looking for fertility and most the women that hormonal imbalance depends on herbal medicine for correction. Hormones is substance that must be required and must be in the right values for reproduction to occur. The aim is this study is to ascertain the Effect of aqueous leave extract of D. alba ness (Thorn Apple) on gonadotropic hormones (FSH, LH) Treated with monosodium glutamate (MSG) and clomiphene citrate in female wistar rats. The animals were randomly selected into 7 with five animals per group. Each group received the following: group 1 10mls/kg of distil water, group 2 low dose of extract (1000mg/kg), group 3 high dose of extract(2000mg/kg), group 4 MSG 800mg/kg, group 5 clomid 50mg/kg, group 6 MSG + high dose of extract and group 7 clomid+ high dose of extract. Administration of extract was done for 21 days, and on the 22nd day, the animals were sacrificed and blood samples were collected for hormonal analysis. The results revealed significant decreased in the serum levels of follicle stimulating hormones (FSH) in all the treatment groups (extract 1000mg/kg, extract 2000mg/kg, MSG 800mg/kg, MSG 800mg/kg + extract 2000mg/kg, and clomid 50mg/kg + extract 2000mg/kg) when compared with control and significant increase in serum levels FSH in clomid 50mg/kg treated group. Luteinizing hormone (LH) serum levels significantly decreased in all the treatment groups when compared with the control group. LH levels in the clomid group significantly increased when compared with other treatment groups. The statistical analysis was carried out using Statistical Package for Social Science (SPSS) version 23.

Immunoreactivity of glutamine synthetase in satellite glia around various subpopulations of lumbar dorsal root ganglia neurons in adult rats treated with monosodium glutamate

Satellite glial cells (SGCs), involved inter alia in glutamate (Glu) metabolism, form a glial sheath around sensory neurons of dorsal root ganglia (DRGs). SGCs show a presence of glutamine synthetase (GS) which transform uptaken Glu into glutamine (Gln). In DRGs, this aminoacid is used mainly by small neurons which are able to synthetize substance P (SP) that play a crucial role in nociception. The aim of the study was to define the influence of monosodium glutamate (MSG) on GS immunoreactivity in satellite glia around various subpopulations of neurons including SP immunopositive cells in DRGs of adult rats. The studies were carried out on lumbar DRGs slides in rats which received subcutaneous injection of saline solution (control group) or 4 g/kg b. w. of MSG (MSG group). Immunofluorescence reactions were conducted with use of anti-GS and anti-SP antibodies. Administration of MSG to adult rats increased the GS immunoexpression in SGCs. In rats receiving MSG, a number of small neurons with GS-immunopositive glial sheath was not altered when compared to control individuals, whereas there was a statistically significant increase of GS immunoexpression in SGCs around large and medium neurons. Moreover, in these animals, a statistically significant increase in the number of small SP-positive neurons with GS-positive glial sheath was observed. SP is responsible for transmission of pain, thus the obtained results may be useful for further research concerning the roles of glia in nociceptive pathway regulation.

Enhancement of hippocampal-dependent spatial memory by Ashwagandha (Withania somnifera) characterized by activation of NMDA receptors against monosodium glutamate-induced neurotoxicity in rats

Background and Aim Monosodium glutamate (MSG) is used in food-additives, and the Food and Drug Administration has placed it under intense scrutiny following several reports that it causes glutamate neurotoxicity. Ashwagandha (ASH) roots are traditionally used for memory enhancement. This study aimed to evaluate the nootropic activity of ASH as well as its therapeutic anti-amnesic activity against MSG-induced hippocampal-dependent spatial memory impairment and hippocampal-NMDAR modulation. Method A total of 36 rats were divided equally into six groups (n = 6 in each group); the rats in the normal and negative groups were administered daily doses of normal saline and MSG (300 mg/kg), respectively, for 21 days. Two nootropic groups were administered ASH at 300 and 500 mg/kg o.p., respectively, for 21 days. Two other treatment groups were administered daily doses of MSG 300 mg/kg o.p. as well as 300 mg/kg and 500 mg/kg o.p. of ASH for 21 days. The rats’ spatial memory was assessed for five days using the MWM. Additionally, NMDAR were measured quantitatively by immunohistochemistry. Results We found that the rats in the nootropic groups showed significantly enhanced nootropic activity characterized by improved hippocampal-dependent spatial memory, as well as increases in the level of NMDAR in the Cornu Ammonis 1 region of their hippocampus. Moreover, we elucidated the therapeutic potential of ASH to protect against the depression of spatial memory caused by MSG-induced neurotoxicity. Conclusion Further, we elucidated a strong correlation between NMDAR-positive cells in the hippocampus and enhancement of spatial learning induced by long-term administration of ASH as well as a strong correlation between NMDAR positive cells in the hippocampus and depression of spatial learning induced by long-term administration of ASH and MSG.

Subchronic Administration of High-dose Monosodium Glutamate Causes Spatial Memory Dysfunction and Structural Deficits of Rat Hippocampus

Introduction: The toxicity of high concentration monosodium glutamate (MSG) has become a controversial issue because of its inconsistent results in human and animal studies. This present study aims to evaluate the effect of subchronic high-doses oral administration of MSG on spatial memory performance and hippocampal pyramidal cells number. Methods: This study involved twenty-eight male Wistar rats, which were divided into a control group of NaCl 0.9% and three intervention groups of MSG 1.0 mg/g bodyweight (M1), 2.0 mg/g bodyweight (M2), and 4.0 mg/g bodyweight (M3) for 30 days. Statistical analysis used a One-way ANOVA test. Results: The result showed significant differences in spatial memory on the Morris Water Maze (MWM) test, including path length (p = 0.020) and escape latency (p = 0.011) according to general linear model repeated measurement analysis. The mean difference of estimated hippocampal pyramidal cells total number among the groups showed volume (p = 0.001), numerical density (p = 0.590), and cells number (p = 0.004). Furthermore, Post-Hoc analysis in both spatial memory and hippocampal pyramidal cells showed that the increasing MSG dose from 1.0 to 4.0 mg/g bodyweight led to a decrease in the results of spatial memory performance on the MWM test and a decrease in hippocampal cells. Conclusion: The present study has provided novel quantitative data that subchronic administration of high-dose MSG caused deleterious effects on the spatial memory function and the volume and number of hippocampal pyramidal cells.

Differential benefits of physical training associated or not with l-arginine supplementation in rats with metabolic syndrome: Evaluation of cardiovascular, autonomic and metabolic parameters

Metabolic syndrome (MetS) is characterized by endocrine-metabolic and cardiac alterations that increase the risk of cardiovascular disease, dyslipidemia, and type-2 diabetes mellitus. Dietary supplementation with l-Arginine (L-Arg) is beneficial for fat loss, while chronic aerobic exercise has several benefits in reversing cardiovascular, autonomic, and metabolic dysfunctions caused by obesity. However, the association between these two approaches has not yet been described. This study aimed to evaluate the possible benefits of physical training, with or without l-Arg-supplementation, on cardiovascular, autonomic, and metabolic parameters in rats with MetS, which was induced by the subcutaneous administration of monosodium glutamate at 4 mg g−1day−1 in rats from the first to fifth day of life. Physical training on a treadmill and supplementation with l-Arg-in adulthood were carried out concomitantly for 8 weeks. After this, the animals underwent femoral artery catheterization to record their cardiovascular parameters and autonomic modulation. Organs and blood were removed to measure levels of nitrite, glucose, and hepatic steatosis. In adult rats with MetS, supplementation with l-Arg-in combination with physical training reduced hypertension, tachycardia, adipose tissue mass, free fatty acids, and hepatic steatosis. Supplementation with l-Arg-and physical training separately was beneficial in reducing several aspects of MetS, but a combination of both was especially effective in reducing adipose tissue and hepatic steatosis. Together, the two therapies can form a good strategy to combat MetS.

Targeting Peripheral N-Methyl-D-Aspartate Receptor (NMDAR): A Novel Strategy for the Treatment of Migraine.

Backgrounds: Several acute and preventive medications were developed for the treatment of migraine. Yet, a significant proportion of patients reports an inadequate response and a lack of tolerability, emphasizing the need for new options. Glutamate is the most important excitatory neurotransmitter in the brain, and glutamate receptors including N-Methyl-D-Aspartate Receptor (NMDAR) are expressed at several levels of the trigeminovascular system, which is the anatomical and physiological substrate of migraine pain. Objective: To review preclinical and clinical studies investigating the role of the NMDAR in migraine pathophysiology. Methods: No protocol was registered for this study. References for the present review were identified from a narrative search of the PubMed database. Search terms such as glutamate, migraine, N-Methyl-D-Aspartate Receptor, and NMDAR were used. No restrictions were made in terms of the language and date of publication. Results: In animal models, administration of monosodium glutamate (MSG) activated and sensitized trigeminovascular neurons. In healthy human participants, consumption of MSG caused headaches, craniofacial sensitivity, and nausea. In in vivo models and through immunolabeling, NMDAR subunits NR1, NR2A, and NR2B were expressed in trigeminal ganglion neurons. In humans, NMDAR antagonists such as ketamine and memantine caused a significant reduction in pain intensity and monthly headache frequency. Conclusions: Accumulative evidence indicates that NMDAR is a promising new target for the treatment of migraine. Selective NMDAR antagonists without central effects are needed to investigate their therapeutic benefit in the treatment of migraine.

The possible protective role of melatonin versus garlic on monosodium Glutamate-induced changes in rat cerebellar cortex: histological, immunohistochemical and electron microscope study

ABSTRACT Monosodium glutamate (MSG) is widely used as a flavor enhancer. Melatonin and garlic are well known as antioxidant. The present study was performed to evaluate the microscopic changes in the cerebellar cortex of rats after the administration of MSG and the possible protective effect of melatonin versus garlic on those changes. The rats were divided into four main groups. Group I (control group). Group II received MSG (4 mg/ g/day). Group III received MSG+ melatonin (10 mg/kg bw/day). Group IV received MSG+garlic (300 mg/kg bw/day). Immunohistochemical staining for glial fibrillary acidic protein (GFAP) was done as a marker for astrocyte demonstration. Morphometric study was done to assess the mean number and diameter of Purkinje cells, the number of astrocytes and the percentage area of positive GFAP immune stain. MSG group demonstrated congested blood vessels, vacuolations in the molecular layer, and Purkinje cells appeared irregular with nuclear degeneration. Granule cells appeared shrunken with darkly stained nuclei. The immunohistochemical stain for GFAP was less than expected in the three layers of the cerebellar cortex. Purkinje cells and granule cells appeared irregular in shape with dark small heterochromatic nuclei. The myelinated nerve fibers showed splitting and loss of the lamellar structure of their myelin sheath. Melatonin group showed that the cerebellar cortex was nearly similar to that of control group. Garlic treated group showed partial improvement. In conclusion, melatonin and garlic could partially protect against MSG induced changes and the protective effect of melatonin was better than garlic.

Effect of monosodium glutamate on fetal development and progesterone level in pregnant Wistar Albino rats

Monosodium glutamate (MSG) is a widespread flavor enhancer and stabilizer in manufactured or packaged foods that possess myriad adverse effects. This study aimed to evaluate the effect of MSG on placental progesterone receptors and fetal development. Thirty pregnant Wistar Albino rats were divided into three groups (ten/each). The control group (G1) gavaged distilled water only, low-dose treated group (G2) gavaged 3 g/kg MSG, and high-dose treated group (G3) gavaged 6 g/kg MSG from 1st to 18th days of gestation, and all pregnant rats were sacrificed on the 19th day of gestation. The effect of MSG on fetal weights, crown vertebral length (CVL), placental weight, placental ghrelin expression, and fetal skeleton examination were estimated. MSG induced a significant decrease in fetal weights, CVL lengths, placental weight, and ghrelin expression in both treatment groups compared to the control group. Several parts of the fetal skeleton showed incomplete ossification and delayed chondrification in which high-dose maternally treated fetuses were more affected. Many degenerative changes were detected in both maternal and fetal liver and kidney tissues in MSG-treated groups. Moreover, MSG caused a significant increase in serum ALT, ALP, and creatinine levels in pregnant rats’ blood. Serum progesterone was only elevated in G3 on the 19th day of gestation. This study showed that the administration of MSG during pregnancy adversely influences fetal growth and skeletal development and caused several biochemical and histological changes in the maternal and fetal liver and kidney tissues which assure the toxic and teratogenic effects of MSG.

Multi-probiotic consumption sex-dependently interferes with MSG-induced obesity and concomitant phagocyte pro-inflammatory polarization in rats: Food for thought about personalized nutrition

Epidemic scope which obesity has reached in many countries necessitates shifting the emphasis in medicine from traditional reaction to individualized and personalized prevention. Numerous trials convincingly prove sexual dimorphism of obesity in morbidity, pathophysiology, comorbidity, outcomes and prophylaxis efficacy. Obesity is characterized by chronic systemic low-grade inflammation that creates the preconditions for the emergence of numerous comorbidities. Leading role in the initiation, propagation and resolution of inflammation belongs to tissue resident and circulating phagocytes. The outcome of inflammation largely depends on phagocyte functional polarization, which in turn is governed by environmental stimuli. Gut microbiota (GM), whose disturbances are one of the key pathogenetic features in obesity, substantially affect phagocyte functions and can either aggravate or calm obesity-associated inflammation. Probiotics possess promising physiological functions, including microbiota-restoring and anti-inflammatory traits, that may possibly help prevent obesity. However, sex-specific effects of probiotic supplementation for targeted obesity prevention remain unknown. The aim of the current study was aimed to compare the effect of multi-probiotic preparation used in prophylactic regimen on the adiposity, profile of culturable GM and its short-chain fatty acids as well as on functional profile of phagocytes from different locations in male and female rats with monosodium glutamate (MSG)-induced obesity. Obesity was induced by neonatal MSG injections in male and female rats, who were given the multi-species probiotic during juvenile and adult developmental stages. Culturable fecal and mucosa-associated microbiota of the intestine were examined using selective diagnostic media. Short-chain fatty acid profile in fecal samples was determined by GC-MS. Phagocyte functional profile was evaluated using flow cytometry and colorimetric methods. Probiotic supplementation after the administration of MSG prevented weight gain and fat accumulation, inflammatory phagocyte activation and alterations in GM in female rats. In male MSG-injected rats, probiotic supplementation restricted but did not prevent weight gain and fat deposition, alleviated but did not prevent systemic inflammation, prevented the alterations in GM, but with residual imbalance in the ratio of obligate anaerobic to facultative anaerobic bacteria. Our findings emphasize the necessity of sex-centered approaches to the prophylactic use of probiotics in obesity in the context of predictive preventive and personalized medicine.

HISTOLOGICAL AND MORPHOLOGICAL CHANGES IN THE LYMPHOID STRUCTURES OF THE GASTRIC MUCOUS MEMBRANE IN WHITE RATS WITH THE ADMINISTRATION OF SODIUM GLUTAMATE.

The aim: To determine the histological and morphological changes of the lymphoid structures of the stomach in male rats under the influence of oral sodium glutamate at the rate of 15 mg/kg of body weight. Materials and methods: The scientific experiment was performed on 20 white non-linear male rats of reproductive age (4-5 months). The experimental animals were divided into two groups (10 rats in each group), which were orally received monosodium glutamate at a dose of 15 mg/kg body weight every day. We studied the effect of 2 and 4 weekly administration of monosodium glutamate at a dose of 15 mg/kg body weight, respectively, in the I and II groups of experimental animals (depending on the week of their decapitation). Rats of the control groups (n=10) were injected with a placebo for 2 and 4 weeks, namely 0.5 ml of dechlorinated tap water at room temperature. Intact control animals were also divided into two groups, 5 rats each, depending on the week of decapitation: respectively, III group - decapitation on the 2nd week of the experiment; IV group - decapitation on the 4th week of the experiment. After the experiments were completed, animals were decapitated under light ether anesthesia. According to the purpose of the study, pieces of rat stomach measuring 1.0 x 1.0 cm were taken from the front wall of the bottom of the stomach near the great curvature, cardiac and portal parts of the organ. Histological preparations were examined using a MICROmed SEO SСAN light microscope and a Vision CCD Camera. Morphometric studies were carried out according to the method of S. B. Stefanov, using grids No. 3/16. For electron microscopic examination, pieces of the stomach wall of rats were fixed in a 2.5% solution of glutaraldehyde in a 0.1 M phosphate buffer (pH 7.2-7.4) with subsequent fixation in a 2.0% solution of osmium tetroxide. After dehydration in alcohols and acetone, the material was embedded in eponaraldite. Sections were made on an LKB-8800-III ultramicrotome and studied using a JEM - 100-V microscope. To study the structural components of the lymphoid formations of the mucous membrane of different parts of the stomach of rats, semi-thin sections were made for the purpose of sharpening the blocks, which were stained with methylene blue. Results: The analysis of the obtained data of the conducted experiment indicates that the administration of monosodium glutamate in a dose of 15 mg/kg of body weight to rats already after 14 days leads to an increase in the density and size of the lymphoid structures of the GMM. The number of immunocompetent cells between the fundus of the gastric glands and the muscle plate increases in the diffuse lymphoid tissue of the gastrointestinal tract of rats in all its parts, both in the I and II groups of experimental animals. These changes are most pronounced in the cardiac and portal parts of the stomach. In both groups of experimental animals, the migration of interepithelial lymphocytes, macrophages, plasma cells, and tissue basophils to the surface epithelium increases. In both groups of experimental animals (and the II group of rats), lymphoid nodules and lymphoid pre-nodules of the gastric mucous membrane (GMM) are located between the bottom of the gastric glands and the muscular plate of the GMM. A gradual increase of medium lymphocytes in the GMM was established both in animals of I and II groups, while large lymphocytes increased in almost the same amount in experimental animals of both groups. Similar changes occur in the characteristics of the number of plasma cells, macrophages and tissue basophils in the lymphoid pre-nodules of GMM. Conclusions: Administering monosodium glutamate to rats at a dose of 15 mg/kg of body weight for 2 weeks leads to an increase in the density and size of lymphoid structures of the mucous membrane in all parts of the stomach with a predominant increase in the number of immunocompetent cells between the bottom of the gastric glands and the muscle plate. At the same time, more pronounced changes were found in the number of small lymphocytes, which tend to decrease by the 2nd week of the experiment, and vice versa - their density increases by the 4th week of monosodium glutamate administration.