MyD88 Deficiency, but Not Gut Microbiota Depletion, Is Sufficient to Modulate the Blood-Brain Barrier Function in the Mediobasal Hypothalamus.

Circumventricular organs (CVOs), including the mediobasal hypothalamus (MBH), have an incomplete blood-brain barrier (BBB). In this study, we determined if the BBB function in the MBH is modulated by the gut microbiota or by the Toll-like receptor (TLR) adapter proteins TRIF or MyD88 signaling. By injecting mice with Evans blue, a marker for BBB permeability, we show that germ-free (GF) and conventionally raised (CONV-R) mice did not differ in the number of Evans blue-positive cells in MBH. Acute modulation of the gut microbiota did not change the number of Evans blue-positive cells. In contrast, CONV-R Myd88-/- and Trif-/- mice had a reduced number of cells in direct contact to the circulation compared to wildtype (WT) mice. This was accompanied by increased tight junction proteins in the blood vessels in Myd88-/- mice. To further characterize the BBB function, we injected WT and Myd88 -/- CONV-R mice as well as WT GF mice with monosodium glutamate (MSG), a neurotoxin that does not cross the BBB. While MSG caused vast cell death in the MBH in CONV-R and GF WT mice, Myd88 -/- mice were protected from such cell death suggesting that fewer cells are exposed to the neurotoxin in the Myd88 -/- mice. Taken together, our results suggest that MyD88 deficiency, but not gut microbiota depletion, is sufficient to modulate the BBB function in the MBH.

Neuroprotective effect of Hydrocotyle sibthorpioides against monosodium glutamate-induced excitotoxicity.

We aimed to evaluate the neuroprotective effect of H. sibthorpioides against monosodium-glutamate (MSG) induced excitoneurotoxicity in rats. We randomly divided the animals into 11 groups (n = 8) and subjected them to high doses of MSG (2 g/kg body weight) and the test dose (1 week). The test chemicals were H. sibthorpioides extracts of petroleum ether, chloroform, methanol, and water. We used Dizocilpine-hydrogen-maleate as a standard and assessed the cognitive property using Morris-water-maze and elevated-plus-maze. After the experimental period, we evaluated the biochemical parameters. We found chloroform and methanolic extracts significantly enhanced the cognitive behaviour of rats compared to control. Biochemical analysis suggested that there was a high level of antioxidants and lower levels of glutamate and proinflammatory cytokines in the cortex and hippocampus. We concluded that chloroform and methanolic extracts of H. sibthorpioides enhanced the level of antioxidants, decreased proinflammatory-cytokines and glutamate in the brain, and thus prevented the monosodium-glutamate-induced-excite-neurotoxicity.

Maternal supplementation of high-value PUFA-Rich Isochrysis sp. biomass prevents monosodium glutamate-induced neurotoxicity in first-generation Wistar rats.

Prenatal supplementation of high-value PUFA (HVPUFA) is essential for adequate brain development in infants. As marine microalgal derived omega-3 fatty acids are considered an alternative source of fish oil, their neuroprotective role on monosodium glutamate (MSG)-induced neurotoxicity, bioavailability, and disease prevention in first-generation (F1) animals need to be explored at molecular level. This study tested the long term supplementation of microalgal derived ω-3 PUFAs from parent rats to its offspring rats and studied the neuroprotective role in monosodium glutamate (MSG)-induced neurotoxicity in F1 rats. The parent animals were divided into three groups: control, microalgal-administered group (5.7 mg of EPA and 1.4 mg of DHA/kg BW from Isochrysis sp.), and fish oil-administered group (4.2 mg of EPA and 2.9 mg of DHA/kg BW derived from fish oil) (FG) and continued up to F1 generation. The F1 male rats from respective parents were separated for disease induction: group I animals (control) were administered with 500 µl of Milli-q water alone and group II (disease control), III (Microalga), and IV (fish oil) animals were administered with 2 g/kg bodyweight of MSG for 10 alternative days. Microalga-treated F1 rats showed significant HDL (43 mg/dl) levels when compared to their experimental groups. Brain tissues of microalga-treated F1 rats (MG) showed higher concentration of DHA (10.1 mg/100 mg tissue) and ARA (18.7 mg/100 mg tissue) levels and significant reduction of MDA (30 nM mg protein) levels. Furthermore, MSG induced neurotoxicity was ameliorated through the activation of CREB and BDNF genes The mRNA expressions of CREB and BDNF were 1.5-fold higher and NMDA levels were 2.0-fold higher in treated groups compared to disease control group. However, the expressions of antioxidant genes (SOD, catalase, and GPX) and apoptotic genes (Bcl-2 and Caspase-3) were significantly reduced in MG treated F1 rats when compared to disease control rats. Histopathological results also showed minimal focal damage in the tissues of MG F1 rats. Prenatal and continuous supply of microalgal biomass improves brain DHA and greatly reduced the consequences of MSG neurotoxicity in F1 rats.

The ameliorative potentials of aqueous leaf extract of Amaranthus hybridus on monosodium glutamate-induced testicular damage in Wistar rats.

OBJECTIVE: Amaranthus hybridus (AH) is a food plant commonly eaten in our country known as a good source of vitamins, minerals, and antioxidants. The present study was designed to investigate the ameliorative potentials of aqueous extract of A. hybridus on Monosodium Glutamate (MSG) -induced testicular toxicity in adult Wistar rats. METHODS: Thirty-two male Wistar rats weighing 160-180 g were divided into four groups. Group A served as control; rats in Group B were given 300 mg/kg of body weight (BW) of aqueous leaf extract of AH; rats in Group C were given 4 mg/g (BW) of 40% MSG; and rats in Group D were given 4 mg/g (BW) of 40% MSG and 300 mg/kg (BW) of extract orally for 6 weeks. RESULTS: There was a significant increase in body weight and a significant reduction in testis weight, testis volume, and testis/body weight ratio in the group given only MSG when compared with controls. Histologically, rats in Groups A and B had normal testicular architecture, while the rats given MSG only showed a significant derangement in testicular histoarchitecture and impaired sperm parameters when compared with controls and the rats given AH. However, these derangements were alleviated in the MSG+AH group when compared with controls. CONCLUSIONS: Aqueous leaf extract of AH ameliorated the testicular derangement resulting from MSG administration.

Protective effects of Rosemary extract and/or Fluoxetine on Monosodium Glutamate-induced hippocampal neurotoxicity in rat.

The use of Monosodium Glutamate (MSG) as a food flavor enhancer is increasing worldwide despite its neurotoxic effects. Fluoxetine (FLX) and Rosemary extract (RE) are known to have beneficial neuroprotective properties. Rats were divided into five groups: control group; MSG group, rats received 2 g∕kg∕day intraperitoneal (i.p.) injections of MSG for seven days; RE/MSG group, rats received 50 mg∕kg∕day of oral RE for 28 days starting prior to MSG; FLX∕MSG group, rats received 10 mg∕kg∕day of oral FLX for 28 days beginning before MSG; and RE∕FLX∕MSG group, received combined treatments as mentioned above. Rats underwent the Barnes maze test, in addition to histopathological, immunohistochemical, morphometric and ultrastructural evaluations for their hippocampi. MSG increased the number of errors and escaped latency in the Barnes maze test that was significantly minimized in the three treatment groups. The MSG group exhibited pyramidal cell (PC) degeneration, shrunken glial cells and massive vascular dilatation that were improved with RE and∕or FLX treatment. The number of glial fibrillary acidic protein (GFAP)-immunopositive cells were increased, and the number of PCs was decreased in the MSG group, while these values were significantly reversed with the three treatment groups with the most significant improvement at RE∕FLX∕MSG one. Ultrastructurally, PCs were shrunken with degenerated nuclei, dilated endoplasmic reticulum, swollen mitochondria, and vacuolations in the MSG group that were improved with RE and∕or FLX. In conclusion, the combined RE and FLX treatment can ameliorate the toxic effect of MSG on rat hippocampus probably through its antioxidant and anti-inflammatory effects.

Akt / GSK3ß / Nrf2 / HO-1 pathway activation by flurbiprofen protects the hippocampal neurons in a rat model of glutamate excitotoxicity.

Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor that regulates redox homeostasis of the cell through regulation of the antioxidant response element genes transcription. Nrf2 also regulates the antiapoptotic Bcl-2 gene. Nrf2 degradation and nuclear translocation is regulated by upstream kinases Akt and GSK3ß. Glutamate excitotoxicity is a process of neuronal cells death due to excessive activation of glutamate receptors. Glutamate excitotoxicity participates in the pathophysiology of several acute and chronic neurological conditions. In addition, glutamate excitotoxicity interrupts the PI3K/Akt prosurvival pathway so GSK3ß remains active. Active GSK3ß increases Nrf2 degradation, decreases Nrf2 nuclear translocation and increases Nrf2 nuclear export which decreases the ARE genes transcription such as, SOD, GSH synthesis enzyme and HO-1. Also, Bcl-2 transcription decreases. Flurbiprofen is a COX inhibitor. Previous studies showed that it has a neuroprotective effect in neurodegeneration and in focal cerebral ischemia/reperfusion model. In our research we aimed to test the hypothesis that flurbiprofen may have a neuroprotective effect in a rat model of glutamate-induced excitotoxicity and this neuroprotection may occur through modulation of (Akt/GSK3ß/Nrf2/HO-1) pathway. Rats were divided into 4 groups; control, MSG (2.5 g/Kg, i.p), low dose FB (5 mg/kg, i.p) and high dose FB (10 mg/kg, i.p). We found that low and high doses FB decreased COX-2, PGE2, NO and MDA and increased SOD and GSH in brain compared to MSG group. High dose was more effective than low dose. Western blotting analysis in hippocampus tissue showed that high dose FB increased p-Akt, p-GSK3ß, nuclear Nrf2 and HO-1 and decreased cytosolic Nrf2 level in comparison with MSG group. Immunohistochemical analysis in hippocampus and cerebral cortex showed that high dose FB increased Bcl-2 and decreased Bax compared to MSG group. In addition, FB increased the number of intact neurons in hippocampus areas and cerebral cortex neurons and showed an anxiolytic-like action in OF and EPM tests. These findings suggest that FB has a neuroprotective effect in glutamate-induced excitotoxicity model through reduction of the glutamate excitotoxicity damage and activation of the survival pathway. These may occur due to modulation the survival pathway (Akt/GSK3ß/Nrf2/HO-1) and inhibition of COX-2.

The effects of L-carnitine on renal function and gene expression of caspase-9 and Bcl-2 in monosodium glutamate-induced rats.

BACKGROUND: Monosodium glutamate (MSG) is frequently consumed as a flavor enhancer or food additive. Possible damages induced by MSG effects on some organs have been stated in experimental animal models. The aim of the present study was to evaluate the protective effects of L-carnitine (L-ca) on the renal tissue in MSG-Induced Rats. METHODS: In this regard, 60 male rats were randomly divided into six groups (n = 10/each): 1 (Control); 2 (sham); 3 (L-carnitine 200 mg/kg b.w); 4 (MSG 3 g/kg b.w); 5 (MSG + L-carnitine 100 mg/kg); and 6 (MSG + L-carnitine 200 mg/kg). After 6 months, the rats were sacrificed, the blood sample collected and the kidneys harvested for evaluation of biochemical analytes, genes expression, and histopathological changes. RESULTS: MSG significantly increased the serum level of MDA, BUN, creatinine, uric acid and renal Caspase-9, NGAL and KIM-1 expression, but it decreased the serum activity also renal expression of SOD, catalase, GPX, and Bcl-2 expression compared to the control group. Treatment with L-ca significantly reduced the serum BUN, creatinine, uric acid and MDA level and increased catalase, GPX and SOD compared to the MSG group. However, only administration of L-ca 200 significantly decreased the caspase-9, NGAL and KIM-1; also, it increased the Bcl-2 expression in the kidney compared to the MSG group. CONCLUSIONS: Our findings indicated that L-carnitine had a major impact on the cell protection and might be an effective therapy in ameliorating the complications of the kidney induced by MSG via its antioxidant and anti-apoptotic properties.

Efficacy of Coccinia grandis against monosodium glutamate induced hepato-cardiac anomalies by inhibiting NF-kB and caspase 3 mediated signalling in rat model.

Since prehistoric times Coccinia grandis has been used as traditional medicine for various diseases including diabetes, dyslipidemia, metabolic and digestive disorders. Although the rationality of efficacy as natural antioxidants with different bioactive compounds in Coccinia grandis against monosodium glutamate (MSG) induced hepato-cardiac damage remains to be disclosed. Six different solvent extracts of the leaves of Coccinia grandis were chosen to evaluate in vitro antioxidant and free radical (FR)-scavenging activity. Due to high antioxidant content and FR-scavenging property of ethanol extract of Coccinia grandis leaves (EECGL) and presence of different bioactive compounds in EECGL was further tested to evaluate in vivo hepato-protective and cardio-protective efficacy against MSG-induced anomalies. MSG-induced dyslipidemia, increased cell toxicity markers altered functional status and histopathological peculiarities of target organs were blunted by EECGL. Additionally, MSG incited increase level of interleukin (IL)-6, tumour necrosis factor (TNF)-α, IL-1ß which activates nuclear factor kappa-B (NF-kB) guided inflammation via down regulation of IL-10; impaired redox-homeostasis subsequently promoted inflammation associated oxidative stress (OS) and increased vascular endothelial growth factor (VEGF) which provoked microvascular proliferation related cellular damage. On the contrary, increased lipid peroxidation and nitric oxide promotes reduced cell viability, deoxyribonucleic acid damage and apoptosis via activation of caspase 3. EECGL significantly reduced MSG-induced inflammation mediated OS and apoptosis via inhibition of pro-inflammatory factors and pro-apoptotic mediators to protect liver and heart. Therefore, it can be suggested that EECGL contributed competent scientific information to validate the demands for its use to treat MSG-induced hepato-cardiac OS mediated inflammation and apoptosis from natural origin.

The neurotherapeutic role of a selenium-functionalized quinoline in hypothalamic obese rats.

RATIONALE: Obesity is considered one of the major global health problems and increases the risk of several medical complications, such as diabetes and mental illnesses. OBJECTIVE: The present study investigated the effect of 7-chloro-4-(phenylselanyl) quinoline (4-PSQ) on obesity parameters, behavioral and neurochemical alterations in hypothalamic obese rats. METHODS: Male Wistar rats received subcutaneous neonatal injections of monosodium glutamate (MSG, 4g/kg) or saline. After the Lee Index evaluation, rats were divided into groups and treated with 4-PSQ (5 mg/kg, intragastric route) or canola oil once a day (post-natal days (PND) 60→76). Open-field, elevated plus-maze, forced swim task, object recognition/location memory, and stepdown inhibitory avoidance tasks were conducted from PND 66 to 74. On PND 76, rats were euthanized and epididymal fat, blood, cerebral cortex, andhippocampus were removed. Blood biochemical parameters and cortical/hippocampal acetylcholinesterase (AChE) and Na /K -ATPase activities were assessed. RESULTS: MSG increased the Lee Index characterizing the chemically induced hypothalamic obesity model. 4-PSQ reversed the increases of epididymal fat, blood glucose, and triglyceride levels caused by MSG exposure. 4-PSQ attenuated anxiety-like and depression-like behaviors induced by neonatal administrations of MSG. Memory deficits found in MSG-obese rats were reversed by treatment with 4-PSQ. Neurochemical alterations produced by MSG evidenced by stimulation ofNa+/K+-ATPase and AChE activities in the cerebral cortex and hippocampus of rats were normalized by 4-PSQ treatment. CONCLUSIONS: In brief, 4-PSQ therapy improved hypothalamic obesity-related parameters, as well as psychiatric symptoms, cognitive impairment, and neurochemical alterations found in obese rats.

Antiapoptotic and antioxidant capacity of phytochemicals from Roselle (Hibiscus sabdariffa) and their potential effects on monosodium glutamate-induced testicular damage in rat.

Monosodium glutamate (MSG), common flavor enhancer and feed additive, causes male reproductive dysfunction. However, Roselle tea, popular Hibiscus sabdariffa (HS) beverage, has a controversial effectiveness on male fertility. Therefore, the current study aimed to investigate either the adverse effect of aqueous HS extract (HSE) on the testicle or its potential ameliorative role including some stress markers, biochemical and immunohistochemical expressions in rats subjected to MSG. Here, the animals were divided into four groups that were given distilled water, HSE, MSG, and HSE + MSG respectively via gavage. After 6 weeks from the beginning of experiment, blood samples were collected for hormonal analysis. Additionally, testicular specimens were excised and processed for oxidative/antioxidant parameters determination, histological examination, and immunohistochemical evaluation of Bax and PCNA positive spermatogenic cells. Preliminary phytochemical analyses as well as antioxidant capacity of the HSE were tested. Our results revealed a strong inhibitory activity of the HSE phytochemical constituents against DPPH radical. MSG group revealed a significant decrease of testosterone, LH, FSH, and antioxidant parameters with elevated MDA compared with control and HSE groups. Additionally, an alteration of the testicular histo-architecture was observed among MSG group along with increased Bax and decreased PCNA positive cells. Meanwhile, the HSE showed a potent protective effect against testicular damage as well as oxidative stress induced by MSG. On the whole, our findings provide evidence that HSE can ameliorate MSG-induced testicular toxicity via induction of cell proliferation along with reduction of oxidative stress and cellular apoptosis in adult rat that attributed to the antioxidant and antiapoptotic effects of its phytochemical constituents.

Physical exercise associated with vitamin D chronic supplementation reduces kidney injury induced by monosodium glutamate.

The aim was to evaluate the effects of chronic vitamin D (VD) supplementation associated with regular swimming over renal histomorphometric aspects in obese rats. Thirty Wistar male rats (5 days old) were used. Twenty four rats were given subcutaneous injections of monosodium glutamate (MSG; 4 g/kg), and six control rats were given an equimolar saline solution. At 21-days-old, the MSG-treated rats were randomly distributed among sedentary animals (S) and exercised (E, swimming; 3x/week). These groups were subdivided into groups orally supplemented with VD (12 µg/kg; 3x/week) or not supplemented (NS), totaling Five experimental groups (n = 6 rats/group): MSG, MSG-SVD, MSG-ENS, MSG-EVD and control groups. In MSG-obese rats, there was such as a decrease in the diameter of the, glomerular tuft, Bowman's capsule, Bowman's space areas, and renal cortical thickness, compared to the control group. In MSG-SVD, MSG-ENS, and MSG-EVD animals, there was an increase in the cortical thickness in relation to the MSG group. In MSG-ENS and MSG-EVD animals, there was a reduction of tubular degeneration in relation to the MSG group. We conclude that physical exercise associated with Vitamin D supplementation can prevent of renal injury, increasing the thickness of the renal cortex and decrease the tubular degeneration.

Zinc oxide nanoparticles with green tea extract complex in the pancreas of rats against monosodium glutamate toxicity.

OBJECTIVES: Nanotechnology is an exciting field for investigators. Green zinc oxide nanoparticles (ZnO NPs) with Camellia sinensis extract complex are proved to be used in the treatment of the toxicity of monosodium glutamate (MSG) in the liver, kidney, and testis of rats. Therefore, the synthesized complex of green nanoparticles using green tea extract (GTE) was tested against the toxicity of MSG on the pancreas. METHODS: The glucose and insulin levels were estimated as well as some biochemical parameters for evaluating the antioxidant status of the pancreas tissue. The histopathological change of the pancreas also has been determined. RESULTS: It indicates the biomedical capability of ZnO NPs/GTE to act as potent antidiabetic through decreasing blood glucose and increasing serum insulin also, inhibition of lipid peroxidation and enhancement of the antioxidant parameters. CONCLUSIONS: The ZnO NPs/GTE enhanced the pancreatic cell and Langerhans islets as well lowered the sugar levels and stimulated insulin.

Ameliorative effect of Nigella sativa oil and vitamin C on the thyroid gland and cerebellum of adult male albino rats exposed to Monosodium glutamate (histological, immunohistochemical and biochemical studies).

Monosodium glutamate (MSG) is a major taste enhancer that is used as a food additive. Vitamin C (Vit C) and Nigella sativa oil (NSO) are known for their potent antioxidant activities. OBJECTIVE: This study investigates the adverse effect of MSG on the thyroid gland and cerebellum of adult male albino rats and the protection against MSG-mediated toxicity provided by Vit C and NSO. DESIGN: Fifty rats were divided into five groups that were treated via oral gavage. Group I (control) rats received distilled water, Group II rats were treated with MSG (6 mg/gm body weight/day), Group III rats were treated with MSG and Vit C (100 mg/kg body weight /day), Group IV rats were treated with MSG and NSO (50 mg/kg body weight two times per week), and Group V rats were treated with MSG together with both Vit C and NSO with MSG. After 60 days of treatment, rats were euthanized and histological sections were prepared from the thyroid gland and the cerebellum for routine staining and immunohistochemical detection of glial fibrillar acidic protein (GFAP), Caspase-3 and proliferating cell nuclear antigen (PCNA), respectively. Cerebellar tissue was also evaluated to determine glutathione (GSH) and malondialdehyde (MDA) levels; GSH was also measured in thyroid tissue. Serum levels of fT3, fT4 and TSH (thyroid stimulating hormone) were also evaluated. RESULTS: Microscopic examination of cerebellar tissues revealed significant cerebellar injury and cellular apoptosis among the rats in Group II. The thyroid glands of Group II rats were notable for degenerating follicles, loss of colloid, sloughed follicular cells and congested blood vessels. The cerebellar and thyroid tissues from rats in treatment Groups III, IV and V revealed significantly less pathology. Cerebellar and thyroid tissues from Group II rats that were treated with MSG alone revealed intense GFAP and caspase-3 (cerebellar) and PCNA (thyroid) immunoreactivity. Furthermore, cerebellar tissues from rats received MSG alone (Group II) were notable for decreased levels of GSH and increased levels of MDA; thyroid tissue from rats in Group II also demonstrated decreased levels of GSH. Likewise, serum fT3 and fT4 levels were significantly decreased, while serum TSH was significantly increased among rats in Group II. Combined administration of Vit C and NSO together with MSG (Group V) revealed some variations in oxidative parameters compared to those in the Group I control rats. CONCLUSIONS: Oral intake of MSG resulted in degenerative changes in neurons and astrocytes in cerebellum and, also degeneration of the thyroid glands of albino rats. Concomitant administration of Vit C and NSO may limit MSG-induced damage to the cerebellum and thyroid glands and thereby provide significant protection against the oxidative damage induced by MSG.

Mechanistic study of attenuation of monosodium glutamate mixed high lipid diet induced systemic damage in rats by Coccinia grandis.

In the context of failure of treatment for non alcoholic fatty liver disease (NAFLD)-mediated systemic damages, recognition of novel and successful characteristic drug to combat these anomalous situations is earnestly required. The present study is aimed to evaluate protective value of ethanol extract of Coccinia grandis leaves (EECGL), naturally occurring medicinal plant, on NAFLD-mediated systemic damage induced by high lipid diet along with monosodium glutamate (HM)-fed rats. Our study uncovered that EECGL significantly ameliorates HM-induced hyperlipidemia, increased lipogenesis and metabolic disturbances (via up regulation of PPAR-α and PPAR-γ), oxidative stress (via reducing the generation of reactive oxygen species and regulating the redox-homeostasis) and inflammatory response (via regulating the pro-inflammatory and anti-inflammatory factors with concomitant down regulation of NF-kB, iNOS, TNF-α and up regulation of eNOS). Furthermore, EECGL significantly inhibited HM-induced increased population of cells in sub G0/G1 phase, decreased Bcl2 expression and thereby loss of mitochondrial membrane potential with over expression of Bax, p53, p21, activation of caspase 3 and 9 indicated the apoptosis and suppression of cell survival. It is perhaps the first comprehensive study with a mechanistic approach which provides a strong unique strategy for the management of HM-induced systemic damage with effective dose of EECGL.

Dietary monosodium glutamate altered redox status and dopamine metabolism in lobster cockroach (Nauphoeta cinerea).

Monosodium Glutamate (MSG) is the most commonly utilized food additive in the world. However, data on possible biochemical reasons underlying the neurotoxic effects of dietary MSG is limited. Therefore, this study investigated the effects of dietary supplementation of MSG on redox status and neurochemical indices in lobster cockroach nymph. These were evaluated via assessment of enzymatic and nonenzymatic antioxidants, acetylcholinesterase and monoamine oxidase activities, and dopamine content in the cockroach nymph head homogenate. MSG supplemented diet caused dose-dependent significant (p < .05) reduction in % survival, thiol, GSH, dopamine contents, and GST activity, increased ROS, NO, Fe2+ , MDA contents, and MAO activity but no significant (p < .05) difference was obtained in GSH and TBARS contents, and AChE activity. Increased oxidative, cholinergic, and monoaminergic activities coupled with decreased dopamine level might be the plausible biochemical explanation for the neurotoxic effects observed during sub-chronic consumption of large amounts of MSG in diet. PRACTICAL APPLICATIONS: This study suggests that consumption of monosodium glutamate should be reduced to the barest minimum due to its capability to induce oxidative stress and nervous toxicological effects at high dosage.

Neuroprotective Potential of Allium sativum against Monosodium Glutamate-Induced Excitotoxicity: Impact on Short-Term Memory, Gliosis, and Oxidative Stress.

This study evaluated the neuroprotective potential of Allium sativum against monosodium glutamate (MSG)-induced neurotoxicity with respect to its impact on short-term memory in rats. Forty male Wistar albino rats were assigned into four groups. The control group received distilled water. The second group was administered Allium sativum powder (200 mg/kg of body weight) orally for 7 successive days, then was left without treatment until the 30th day. The third group was injected intraperitoneally with MSG (4 g/kg of body weight) for 7 successive days, then left without treatment until the 30th day. The fourth group was injected with MSG in the same manner as the third group and was treated with Allium sativum powder in the same manner as the second group, simultaneously. Phytochemical analysis of Allium sativum powder identified the presence of diallyl disulphide, carvone, diallyl trisulfide, and allyl tetrasulfide. MSG-induced excitotoxicity and cognitive deficit were represented by decreased distance moved and taking a long time to start moving from the center in the open field, as well as lack of curiosity in investigating the novel object and novel arm. Moreover, MSG altered hippocampus structure and increased MDA concentration and protein expression of glial fibrillary acidic protein (GFAP), calretinin, and caspase-3, whereas it decreased superoxide dismutase (SOD) activity and protein expression of Ki-67 in brain tissue. However, Allium sativum powder prevented MSG-induced neurotoxicity and improved short-term memory through enhancing antioxidant activity and reducing lipid peroxidation. In addition, it decreased protein expression of GFAP, calretinin, and caspase-3 and increased protein expression of Ki-67 in brain tissues and retained brain tissue architecture. This study indicated that Allium sativum powder ameliorated MSG-induced neurotoxicity through preventing oxidative stress-induced gliosis and apoptosis of brain tissue in rats.

African walnuts attenuate ectopic fat accumulation and associated peroxidation and oxidative stress in monosodium glutamate-obese Wistar rats.

AIMS: African walnuts were previously shown to modulate hepatic lipid bio-accumulation in obesity. Herein, we investigated the impact of the nuts on fat accumulation in adipose and ectopic regions, and associated oxidatiive stress status in obese rats. MATERIALS AND METHODS: Whole ethanol extract (WE) of the nuts, and its liquid-liquid fractions-ethyl acetate (ET) and residue (RES) were separately administered to obese rats for 6 weeks. The normal (NC) and obese (OC) controls received normal saline and the standard control (SC), orlistat (5.14 mg/kg b.w.), during the same period. Thereafter, the animals were euthanized and the adipose, brain, kidneys and heart tissues were studied. RESULTS: The change in body weight to naso-anal length which increased by 63.52 % in OC compared to NC (p < 0.05), decreased by 57.88, 85.80 and 70.20 % in WE, ET and RES-treated groups, respectively, relative to the OC (p < 0.05). Also, adipose tissue weights were lowered upon treatment with the extracts and fractions versus OC (p < 0.05). Total lipids, phospholipids, triacylglycerol and cholesterol concentrations in the studied tissues which were higher in OC (p < 0.05) were lowered (p < 0.05) and compared favorably with SC. Further, malondialdehyde levels in the tissues were lowered upon treatment, compared to the OC (p < 0.05). Glutathione level and activities of glutathione peroxidase, superoxide dismutase and glutathione-S-transferase which were decreased (p < 0.05) in OC, were restored upon treatment with the extracts, relative to the obese control (p < 0.05). SIGNIFICANCE: African walnuts assuaged lipogenesis, oxidative stress and peroxidation in extra-hepatic tissues of obese rats, hence, may attenuate ectopic fat accumulation and its associated pathogenesis.

Ameliorative Role of Green Tea and Zinc Oxide Nanoparticles Complex Against Monosodium Glutamate-Induced Testicular Toxicity in Male Rats.

BACKGROUND AND OBJECTIVE: This study was designed to estimate the long-term effects of zinc oxide nanoparticles/green tea (ZnONPs/GTE) complex against monosodium glutamate (MSG). The antioxidant/oxidative status, testosterone levels, DNA damage, and histopathological changes of testis were evaluated. METHODS: The rats were divided into eight groups that were treated as follows: saline, the lower dosage of MSG (6.0 mg/kg), the higher dosage of MSG (17.5 mg/Kg), GTE, ZnONPs, ZnONPs/GTE and the last two groups were treated with the lower dosage of MSG or the higher dosage of MSG with ZnONPs/GTE complex. The data showed minimal toxicity in testicular tissue after the administration of ZnONPs. RESULTS: The MSG treatment in the adult male rats reduced testosterone levels and disrupted testicular histology, which revealed dose-dependence of MSG. Also, ZnONPs induced testicular dysfunction through the interference of antioxidant/oxidant balance and suppression of testosterone levels as well as induction of cellular damage of testis. The combination of ZnONPs with GTE complex significantly protects against MSG or ZnONPs toxicity by decreasing the DNA damage, oxidative stress, and enhancement of antioxidant as well as histological structure of testis. CONCLUSION: We could recommend using ZnONPs/GTE complex to reduce the toxicity of ZnONPs and MSG on the testis at the cellular and oxidative stress levels.

Coconut Water Prevents Renal and Hepatic Changes in Offspring of Monosodium Glutamate-Treated Wistar Rat Dams.

Monosodium glutamate (MSG) is a widely-consumed taste enhancer which has been implicated in the aetiology of renal and hepatic dysfunction in adults and their offspring. There is increasing evidence on the therapeutic properties of Coconut Water (CW) in kidney and liver disorders. This study investigated the effects of CW on renal and hepatic functions in offspring of MSG-fed dams. Twelve female Wistar rats (120 - 140 g) were grouped into four as follows; Control (10 ml/Kg distilled water), MSG (0.08 mg/Kg), CW (10 ml/Kg) and MSG+CW. Treatments were given orally daily commencing two weeks prior to mating, throughout mating and gestation until parturition. All dams received standard rodent diet and drinking water ad libitum throughout the study. After weaning on Post-Natal Day (PND) 28, serum was obtained from offspring for assay of liver and renal function. Histological analysis of the livers and kidneys were performed on both dams and offspring. There was no significant difference in liver enzymes, urea, creatinine and albumin levels amongst the offspring on PND 28. However, liver and kidney sections from MSG dams and their offspring showed early degenerative changes which were not evident in renal and hepatic tissues from CW and MSG+CW dams and offspring. These observations suggest that coconut water protects against monosodium glutamate-induced renal and hepatic dysfunction in dams and offspring.

Evaluation of the Effect of Nanoparticles Zinc Oxide/Camellia sinensis Complex on the Kidney of Rats Treated with Monosodium Glutamate: Antioxidant and Histological Approaches.

BACKGROUND: Zinc oxide nanoparticles (ZnO NPs) are robustly used biomedicine. Moreover, no study has been conducted to explore the consequence of green synthesis of ZnO NPs with Camellia sinensis (green tea extract, GTE) on kidneys of rats treated with monosodium glutamate (MSG). METHODS: Therefore, the objective of the research was designed to explore the possible defensive effect of GTE/ZnO NPs against MSG-induced renal stress investigated at redox and histopathological points. RESULTS: The levels of urea and creatinine increased as the effect of a high dose of MSG, in addition, the myeloperoxidase and xanthine oxidase activates were elevated significantly with the high dose of MSG. The levels of non-enzymatic antioxidants (uric acid, glutathione, and thiol) were decreased sharply in MSG-treated rats as compared to the normal group. CONCLUSION: The data displayed that GTE/ZnO NPs reduced the effects of MSG significantly by reduction of the level peroxidation and enhancement intracellular antioxidant. These biochemical findings were supported by histopathology evaluation, which showed minor morphological changes in the kidneys of rats.