Quercetin counteracts monosodium glutamate to mitigate immunosuppression in the thymus and spleen via redox-guided cellular signaling.

BACKGROUND: Chronic inflammation brought on by oxidative stress can result in several immunopathologies. Natural compounds with antioxidant characteristics, like quercetin, have shown effectiveness in reducing oxidative damage and regulating the immune response. PURPOSE: The commonly used food additive monosodium glutamate (M) causes immunosuppression by disrupting redox equilibrium and inducing oxidative stress. The goal of this work is to examine the therapeutic potential of quercetin against immunotoxicity brought on by M, revealing the molecular route implicated in such immunopathology by targeting the thymus and spleen, to support the development of future anti-inflammatory and antioxidant therapies. STUDY DESIGN AND METHODS: M-fed rats were employed as an immunotoxicity model and were supplemented with quercetin for four weeks. Hematological and biochemical parameters were measured; H&E staining, immunohistochemistry, flow cytometry, real-time quantitative PCR, and western blotting were performed. RESULTS: Based on the findings, TLR4 was activated by M to cause oxidative stress-mediated inflammation, which was alleviated by the supplementation of quercetin by modulating redox homeostasis to neutralize free radicals and suppress the inflammatory response. To prevent M-induced inflammation, quercetin demonstrated anti-inflammatory functions by blocking NF-kB activation, lowering the production of pro-inflammatory cytokines, and increasing the release of anti-inflammatory cytokines. By normalizing lipid profiles and lowering the potential risk of immunological deficiency caused by M, quercetin also improves lipid metabolism. Additionally, it has shown potential for modifying insulin levels, suggesting a possible function in controlling M-induced alteration in glucose metabolism. The addition of quercetin to M enhanced the immune response by improving immunoglobulin levels and CD4/CD8 expression in the thymus and spleen. Additionally, quercetin inhibited apoptosis by controlling mitochondrial caspase-mediated cellular signaling, suggesting that it may be able to halt cell death in M-fed rats. CONCLUSION: The results of this study first indicate that quercetin, via modulating redox-guided cellular signaling, has a promising role in reducing immune disturbances. This study illuminates the potential of quercetin as a safe, natural remedy for immunopathology caused by M, including thymic hypoplasia and/or splenomegaly, and paves the way for future anti-inflammatory and antioxidant supplements.

The low glutamate diet reduces blood pressure in veterans with Gulf War Illness: A CONSORT randomized clinical trial.

BACKGROUND: Gulf War Illness is a multi-symptom condition affecting veterans of the 1990 to 1991 Gulf War, which often presents with comorbid hypertension. The purpose of this study was to analyze the effects of the low glutamate diet, as well as an acute challenge of monosodium glutamate (MSG)/placebo, on resting heart rate, blood oxygenation level, and blood pressure (BP) in this population. METHODS: These data were measured at 4 time points: baseline, after 1 month on the low glutamate diet, and during each challenge week, where subjects were randomized into a double-blind, placebo-controlled, crossover challenge with MSG/placebo over 3 days each week. Pre-post diet changes were analyzed using paired t tests, change in the percentage of veterans meeting the criteria for hypertension was compared using chi-square or Fisher exact tests, and crossover challenge results were analyzed using general linear modeling in SAS® 9.4. RESULTS: There was a significant reduction in systolic BP (sitting and recumbent; both P < .001) and diastolic BP (sitting; P = .02) after 1 month on the diet. The percentage meeting the criteria for hypertension was also significantly reduced (P < .05). Challenge with MSG/placebo did not demonstrate an acute effect of glutamate on blood pressure. CONCLUSION: Overall, these findings suggest that the low glutamate diet may be an effective treatment for lowering blood pressure in veterans with Gulf War Illness. This dietary effect does not appear to be driven by reduced consumption of free glutamate, but rather, by an increase in consumption of non-processed foods.

Effects of the food additive monosodium glutamate on cisplatin-induced gastrointestinal dysmotility and peripheral neuropathy in the rat.

BACKGROUND: Cisplatin is an antineoplastic drug known to produce intense vomiting, gastric dysmotility, and peripheral neuropathy. Monosodium glutamate (MSG) is a flavor enhancer with prokinetic properties potentially useful for cancer patients under chemotherapy. Our aim was to test whether MSG may improve gastrointestinal motor dysfunction and other adverse effects induced by repeated cisplatin in rats. METHODS: Male Wistar rats were exposed or not to MSG (4 g L-1 ) in drinking water from week 0 to 1 week after treatment. On the first day of weeks 1-5, rats were treated with saline or cisplatin (2 mg kg-1  week-1 , ip). Gastrointestinal motility was measured by radiological methods after first and fifth administrations, as well as 1 week after treatment finalization. One week after treatment, the threshold for mechanical somatic sensitivity was recorded. Finally, samples of stomach, terminal ileum and kidneys were evaluated in sections using conventional histology. The myenteric plexus was immunohistochemically evaluated on distal colon whole-mount preparations. KEY RESULTS: Monosodium glutamate prevented the development of cisplatin-induced neuropathy and partially improved intestinal transit after the fifth cisplatin administration with little impact on gastric dysmotility. MSG did not improve the histological damage of gut wall, but prevented the changes induced by cisplatin in the colonic myenteric plexus. CONCLUSION AND INFERENCES: Our results suggest that MSG can improve some dysfunctions caused by anticancer chemotherapy in the gut and other systems, associated, at least partially, with neuroprotectant effects. The potentially useful adjuvant role of this food additive to reduce chemotherapy-induced sequelae warrants further evaluation.

Excitotoxicity triggered by neonatal monosodium glutamate treatment and blood-brain barrier function.

It is likely that monosodium glutamate (MSG) is the excitotoxin that has been most commonly employed to characterize the process of excitotoxicity and to improve understanding of the ways that this process is related to several pathological conditions of the central nervous system. Excitotoxicity triggered by neonatal MSG treatment produces a significant pathophysiological impact on adulthood, which could be due to modifications in the blood-brain barrier (BBB) permeability and vice versa. This mini-review analyzes this topic through brief descriptions about excitotoxicity, BBB structure and function, role of the BBB in the regulation of Glu extracellular levels, conditions that promote breakdown of the BBB, and modifications induced by neonatal MSG treatment that could alter the behavior of the BBB. In conclusion, additional studies to better characterize the effects of neonatal MSG treatment on excitatory amino acids transporters, ionic exchangers, and efflux transporters, as well as the role of the signaling pathways mediated by erythropoietin and vascular endothelial growth factor in the cellular elements of the BBB, should be performed to identify the mechanisms underlying the increase in neurovascular permeability associated with excitotoxicity observed in several diseases and studied using neonatal MSG treatment.

Dietary free glutamate prevents diarrhoea during intra-gastric tube feeding in a rat model.

Recent studies indicate that l-glutamate (l-Glu), abundant in many foods, is a stimulator of gastric vagal afferent nerves. The aim of the present study was to examine the possibility that l-Glu supplementation of a protein-rich liquid diet may prevent the incidence of diarrhoea during repetitive intra-gastric tube feeding. The gastric vagal afferent nerve recording of rats indicated that intra-gastric administration of a protein-rich liquid diet supplemented with 0·5 % monosodium glutamate enhanced the basal afferent activities seen with the protein-rich diet alone. The examination of the faeces showed that the addition of monosodium glutamate to the liquid diet significantly prevented the incidence of diarrhoea induced by repetitive gastric feeding. In conclusion, supplementation of an enteral liquid diet with free l-Glu may ameliorate diarrhoea during intra-gastric tube feeding by sending visceral glutamate information from the stomach to the brain.

Caracterização de crianças portadoras de câncer segundo sensibilidade ao umami e consumo alimentar / Characterization of children with cancer according to sensitivity to umami and food consumption

Introdução: A Leucemia Linfóide Aguda (LLA) e o Linfoma não-Hodgkin (LNH) são os tipos de câncer mais incidentes em crianças e a ingestão alimentar pode ser diminuída pela quimioterapia. A sensação do gosto é resultante da detecção e resposta ao estímulo doce, salgado, azedo, amargo e umami. Esse último, identificado pelo glutamato monossódico (MSG), é relacionado ao aumento da palatabilidade, o que pode colaborar para a melhora da aceitação alimentar em crianças com câncer. Objetivo: Identificar os limiares de detecção do gosto umami e a qualidade da alimentação em crianças portadoras de LLA e LNH. Metodologia: Foi aplicado teste de sensibilidade de Threshold para determinar o limiar do gosto umami, com 6 concentrações crescentes de água deionizada e MSG. Aplicou-se recordatório 24 horas e questionário de frequência alimentar para avaliar o consumo alimentar. O peso e altura foram mensurados e IMC utilizados para classificação do estado nutricional, segundo o National Center for Health Statistics (2000). Caracterizou-se a amostra através da distribuição de frequência das variáveis, com auxílio do pacote estatístico Epinfo Versão 6.0. As análises estatísticas e gráficas foram feitas no software R, versão 2.6.2. Foi realizado teste de Cluster para caracterizar a amostra. Resultados: Dos 102 pacientes, 94 eram sensíveis ao umami. 54,3 por cento do sexo masculino e 45,7 por cento do feminino. 78,4 por cento portadores de LLA e 21,6 por cento de LNH. 91,0 por cento em fase de manutenção. Quanto à idade, 38,3 por cento entre 6 e 7 anos; 20,6 por cento entre 8 e 9; 15,7 por cento entre 10 e 11; 15,7 por cento entre 12 e 13 e 9,8 por cento 14 anos. 8,5 por cento apresentaram baixo peso, 66,0 por cento eutrofia e 25,5 por cento sobrepeso ou obesidade. O produto rico em glutamato monossódico mais consumido foi macarrão instantâneo. O molho inglês e de soja foram os menos consumidos...

Contribution of umami taste substances in human salivation during meal.

The oral gustatory perception during a meal has very important physiological roles such as inducing appetite, smoothing mastication and swallowing, promoting digestion and each nutrient availability. One hundred years ago, L-glutamate was discovered as a new taste substance in Japan. Since then, Japanese taste physiologists have lead the research to establish L-glutamate as the prototype molecule for the fifth basic taste (umami taste), in addition to saltiness, sweetness, bitterness and sourness. Meanwhile, various lines of evidence demonstrated that taste perception is linked to taste stimuli-oral/pharyngeal reflexes. In this review, we focus on the efficacy of L-glutamate for human salivation and discuss the possible application of umami taste simulation to the nutritional management for the elderly due to amelioration of their quality of life (QOL).

The effect of Na-glutamate treatment on enzyme- and bioelectric activities in rat brain.

Endogenous and exogenous Na-glutamate (Glu) accumulation in central nervous system (CNS) may be involved in neuronal death, leading to neurodegenerative disorders in humans. This paper describes the effect of in vivo and in vitro Glu treatment on rat bioelectric activity in hypothalamus (HT) and cerebral cortex (C), as well as the measurement of brain enzyme activities involved in the metabolism and transport of Glu in brain cells.Glu may be a key factor in the onset of neuronal cell death by changing the cell energetics, the cellular redox-potential, due to a decreased free radical scavenging capacity.

Postnatal monosodium glutamate treatment results in attenuation of corticosterone metabolic rate in adult rats.

OBJECTIVE: To study the basal and ACTH stimulated production of corticosterone by adrenal cortex on one hand and the binding and degradation of corticosterone in the liver of adult rats which were treated with monosodium glutamate (MSG) during the neonatal period. METHODS: Male offsprings of Sprague-Dawley rats were injected i.p. with MSG (4 mg/g of b.w. in saline) on alternated days for the first 10 days of life, their littermates being used as controls. On the 21st postnatal day they were weaned and used for the observation at the age of 65-75 days. After sacrifice the level of corticosterone in serum and the release of corticosterone from incubated adrenals under basal and ACTH stimulated conditions (ACTH in 6 concentrations from 1.25 to 80 mU/ml medium) were estimated. In addition, glucocorticoid binding to cytosol receptors in the liver and muscle tissues was determined. Corticosterone degradation rate was measured by decrease of corticosterone concentration added to the medium after the incubation with liver slices. RESULTS: Adult rats neonatally treated with MSG had reduced weight of adrenal glands, while plasma corticosterone levels and its basal production by adrenals in vitro were significantly higher than in controls. In MSG treated rats the stimulation of corticosterone production by ACTH was diminished. Glucocorticoid binding to liver cytosolic receptors was significantly decreased, while that in muscle tissue was only slightly elevated. Moreover, a decreased corticosterone degradation rate in liver slices was observed in rats treated neonatally with MSG. CONCLUSIONS: These results are in agreement with previously observed decrease of corticosterone clearance rate in MSG treated animals and suggest that elevated corticosterone levels in plasma and its prolonged response to stressogenic stimulation are due to elevated corticosterone production in adrenals and lower degradation rate in the liver.

[Lipid peroxidation and various parameters of mineral metabolism in patients with alimentary obesity during therapy with monosodium glutamate]. / Issledovanie perekisnogo okisleniia lipidov i nekotorykh pokazatelei mineral'nogo obmena u bol'nykh alimentarnym ozhireniem pri ispol'zovanii v dietoterapii mononatriia glutamata.

Lipid peroxidation and mineral metabolism were studied in patients with III degree of obesity and bad standing of sodium restricted diet before and after treatment with including in diet of monosodium glutamate (MSG). It was established well being of MSG and absence of negative effect on loss of body mass in course of dietary treatment. MSG caused normalization of level of diene conjugates and some minerals in serum of patients.

[Effect of glutamate and combined with inosine monophosphate on gastric secretion]. / Deistvie glutamata i ego sochetaniia s inozinmonofosfatom na zheludochnuiu sekretsiiu.

Experiments on dogs with Pavlov pouch and gastric fistula demonstrate that monosodium glutamate (MSG) enriched with inosine monophosphate (IMP) potentiate pentagastrin-induced gastric secretion. The preparation (Chi-Mi) was introduced directly into the intestine through a fistula. When given alone in an equal quantity MSG produced the same effect. In per os administration Chi-Mi was more effective, probably due to a different response of the gustatory receptors to MSG and Chi-Mi. When the latter two were added to meat used as a food stimulus, Chi-Mi brought about more intensive gastric secretion in all its phases. In sham feeding Chi-Mi also intensified the secretion augmenting the reflex phase of gastric secretion when added to food substances. The findings may appear helpful in further search for medical application of glutamate and allied substances.

Antiischemic and metabolic effects of glutamate during pacing in patients with stable angina pectoris secondary to either coronary artery disease or syndrome X.

The effects of glutamate on anginal threshold, cardiac metabolism and hemodynamics were studied in 11 patients with stable angina pectoris, positive stress test results, and pacing-induced myocardial lactate release due to coronary artery disease (CAD) (n = 9) or syndrome X (n = 2). Data were obtained before, during and after 2 identical periods of coronary sinus pacing, the second being preceded by an intravenous injection of monosodium glutamate 1.2 (n = 7) or 2.5 (n = 4) mg/kg body weight. After glutamate administration, pacing time to onset of angina increased from mean +/- standard deviation 103 +/- 53 to 166 +/- 71 seconds (p less than 0.01) and ST-segment depression after pacing decreased from 2.3 +/- 1.0 to 1.6 +/- 1.1 mm (p less than 0.01). Arterial glutamate concentration increased 60% (p less than 0.01) after the low dose and 150% (p less than 0.01) after the high dose of glutamate. Regardless of dose, myocardial glutamate uptake increased by 25% (p less than 0.01). Pacing-induced cardiac release of lactate diminished 50% (p less than 0.05), whereas the releases of xanthine and hypoxanthine were unchanged by glutamate. Arterial free fatty acids decreased 20% (p less than 0.01). Circulating levels and cardiac exchanges of alanine, glucose and citrate were unchanged. Glutamate did not influence heart rate, arterial blood pressure, coronary blood flow, coronary vascular resistance or myocardial oxygen consumption. One patient complained of short-lasting burning sensations after receiving the high glutamate dose. In conclusion, augmented provision of glutamate enhances pacing tolerance in stable angina, presumably by a metabolic improvement of cardiac energy production during ischemia.

[Potentiating effect of sodium glutamate on gastric secretion and its possible use as a clinical test]. / Potentsiruiushchee deistvie glutamata natriia na zheludochnuiu sekretsiiu i ego vozmozhnoe ispol'zovanie v kachestve klinicheskogo testa.

The authors report a potentiating effect of sodium glutamate on gastric secretion in subjects free of gastrointestinal diseases. Similar effect has been discovered in dogs. In subjects with gastric hyposecretion (chronic gastritis, functional regulatory disturbances) sodium glutamate combined with pentagastrin is a helpful tool in overall evaluation of gastric secretion. In achlorhydria is can be used for determination of a residual capacity of the stomach to secrete the hydrochloric acid in failure of humoral stimulators.

Decreased incidence of diabetes mellitus by monosodium glutamate in the non-obese diabetic (NOD) mouse.

Subcutaneous administration of monosodium glutamate (MSG) to neonatal female non-obese diabetic (NOD) mice resulted in obesity associated with stunting and hyperinsulinemia. However, the cumulative incidence of diabetes mellitus at 25 weeks of age in the MSG group was significantly lower than in the control group (10.3% vs. 43.6%, P less than 0.005). The immunoreactive insulin content of the pancreas from the 13- to 20-week-old MSG-treated mice was higher than that of the control mice (P less than 0.005). Immunohistochemistry showed that the number of pancreatic B-cells was well preserved and insulitis was attenuated in the MSG-treated mice. Plasma corticosterone and 3, 5, 3'-triiodothyronine levels were elevated in the MSG group. These results suggested that, by the MSG treatment, the B-cell functions were maintained through the modification of the degenerative process of the islets in the NOD mouse.

Reduced norepinephrine turnover in brown adipose tissue of pre-obese mice treated with monosodium-L-glutamate.

Norepinephrine (NE) turnover, an index of sympathetic nervous system (SNS) activity, was measured in interscapular brown adipose tissue (IBAT), heart and pancreas of 3-weeks-old pre-obese monosodium-L-glutamate (MSG) mice and at 6-weeks-old mildly obese MSG mice. In IBAT, rates of NE turnover were slower not only in 3-weeks-old MSG mice but also in older obese MSG mice than in their saline controls. In heart, rates of NE turnover were slower in 6-weeks-old mildly obese MSG mice, but not in pre-obese MSG mice. No significant difference in NE turnover in pancreas was observed at either age. The low NE turnover in IBAT of MSG-treated mice prior to the onset of gross obesity suggests that low SNS activity may be an initial contributor to their high energy efficiency and resultant obesity.

Effects of neonatal treatment with monosodium-glutamate in spontaneously hypertensive rats.

Following neonatal treatment with monosodium-glutamate (MSG), blood pressure in adult spontaneously hypertensive rats (SHR) was markedly lower than in control SHR, with only a small decrease in normotensive Wistar-Kyoto controls (WKY). In addition, in MSG-treated SHR an increase in pain-sensitivity was found and both strains showed increased water intake and reduced organ and body weights as compared to vehicle-treated rats.

A further experimental study of the antisilicotic effect of glutamate.

Two groups of rats were exposed to quartz dust for six months and in addition one group was given drinking water containing 1.5% sodium glutamate while the second received only water. In the rats receiving glutamate we observed (a) evidence for a considerably reduced cytotoxic effect of the quartz on cells obtained by bronchopulmonary lavage, (b) a reduction in dust retention in the lungs, especially in the tracheobronchial lymph nodes, (c) a considerable reduction in the weight gain in the lungs and in their hydroxyproline and lipid contents, and (d) the inhibition of the formation of silicotic nodules. Polarographic studies of the oxygen consumption of peritoneal macrophages from rats receiving glutamate showed that glutamate prevents the adverse effects of quartz on mitochondrial oxidative processes.