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.

Unlocking Nature's Toolbox: glutamate-inducible recombinant protein production from the Komagatella phaffii PEPCK promoter.

BACKGROUND: Komagataella phaffii (a.k.a. Pichia pastoris) harbors a glutamate utilization pathway in which synthesis of glutamate dehydrogenase 2 and phosphoenolpyruvate carboxykinase (PEPCK) is induced by glutamate. Glutamate-inducible synthesis of these enzymes is regulated by Rtg1p, a cytosolic, basic helix-loop-helix protein. Here, we report food-grade monosodium glutamate (MSG)-inducible recombinant protein production from K. phaffii PEPCK promoter (PPEPCK) using green fluorescent protein (GFP) and receptor binding domain of SARS-CoV-2 virus (RBD) as model proteins. RESULTS: PPEPCK-RBD/GFP expression cassette was integrated at two different sites in the genome to improve recombinant protein yield from PPEPCK. The traditional, methanol-inducible alcohol oxidase 1 promoter (PAOX1) was used as the benchmark. Initial studies carried out with MSG as the inducer resulted in low recombinant protein yield. A new strategy employing MSG/ethanol mixed feeding improved biomass generation as well as recombinant protein yield. Cell density of 100-120 A600 units/ml was achieved after 72 h of induction in shake flask cultivations, resulting in recombinant protein yield from PPEPCK that is comparable or even higher than that from PAOX1. CONCLUSIONS: We have designed an induction medium for recombinant protein production from K. phaffii PPEPCK in shake flask cultivations. It consists of 1.0% yeast extract, 2.0% peptone, 0.17% yeast nitrogen base with ammonium sulfate, 100 mM potassium phosphate (pH 6.0), 0.4 mg/L biotin, 2.0% MSG, and 2% ethanol. Substitution of ammonium sulphate with 0.5% urea is optional. Carbon source was replenished every 24 h during 72 h induction period. Under these conditions, GFP and RBD yields from PPEPCK equaled and even surpassed those from PAOX1. Compared to the traditional methanol-inducible expression system, the inducers of glutamate-inducible expression system are non-toxic and their metabolism does not generate toxic metabolites such as formaldehyde and hydrogen peroxide. This study sets the stage for MSG-inducible, industrial scale recombinant protein production from K. phaffii PPEPCK in bioreactors.

Effects of vincristine and monosodium glutamate on gastrointestinal motility and visceral sensitivity.

BACKGROUND: Chemotherapy-induced adverse effects are an unresolved nightmare. In preclinical studies in rats, the food additive monosodium glutamate (MSG) improved some of the side effects caused by cisplatin, but its effects in other models of chemotherapy-treated animals are not well known. The aim of this study was to test if MSG may improve some of the adverse effects induced by vincristine in rats. METHODS: Young male Wistar rats were exposed or not to MSG (4 g L-1 ) in drinking water from week 0 till 1 week after treatment (week 3). Rats received two cycles of five daily intraperitoneal (ip) injections (Monday to Friday, weeks 1 and 2) of either saline (2 mL kg-1 ) or vincristine (0.1 mg kg-1 ). Gastrointestinal motility was measured in vivo by radiological methods after the first and tenth ip administrations. On week 3, the threshold for mechanical somatic and colorectal sensitivity was recorded using Von Frey filaments applied to the paws and an intracolonic balloon, respectively. Finally, samples of the terminal ileum and distal colon were histologically evaluated in sections. KEY RESULTS: Vincristine reduced body weight gain, food intake, and upper gastrointestinal transit, caused somatic (but not visceral) hypersensitivity and increased the thickness of the submucosal and muscle layers of the small intestine. In vincristine-treated animals, MSG partially prevented gastrointestinal dysmotility and reduced visceral sensitivity but did not improve structural alterations of the small intestine. CONCLUSIONS & INFERENCES: MSG could be used as an adjuvant to conventional treatments to improve some gastrointestinal dysfunctions caused by chemotherapy.

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

OBJECTIVE: 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. PATIENTS AND METHODS: 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: 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. CONCLUSION: 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.

Potential Defence Mechanisms Triggered by Monosodium Glutamate Sub-Chronic Consumption in Two-Year-Old Wistar Rats.

Monosodium glutamate (MSG) is the sodium salt of glutamic acid (GLA), used as a flavour enhancer. MSG is considered a controversial substance. It is incriminated in disturbing the antioxidant system, but also has beneficial effects, as GLA metabolism plays a crucial role in homeostasis. This study highlights which positive or negative aspects of MSG sub-chronic consumption are better reflected in subjects potentially affected by advanced age. Daily doses of MSG were administered to four groups of two-year-old Wistar rats for 90 days: (I) 185 mg/kg bw, (II) 1500 mg/kg bw, (III) 3000 mg/kg bw and (IV) 6000 mg/kg bw, compared to a MSG non-consumer group. Aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, direct and total bilirubin, total cholesterol, triglycerides, creatinine and urea levels were analysed; stomach, liver and kidney samples were subjected to histopathological analysis. Although, in most cases, there were no statistical differences, interesting aspects of the dose-effect relationship were observed. After MSG sub-chronic consumption, the positive aspects of GLA seem to be reflected better than the negative ones. The hormesis effect, with low-level reactive oxygen species' protective effects and GLA metabolism, may represent the hypothesis of a potential defence mechanism triggered by MSG sub-chronic consumption in ageing rats.

Effect of Addition of Umami and Sour Components on NaCl Taste in Humans.

We investigated the effects of adding umami and sour components to the taste characteristics of NaCl (75 mM and 100 mM) using sensory evaluation. Here, we employed a mixture of 1 mM monosodium glutamate (MSG) and 0.5 mM inosine 5'-monophosphate (IMP) as the umami component and 3 mM citric acid as the sour component. We confirmed that the addition of MSG+IMP significantly enhanced the salty taste intensity of the NaCl solutions. In addition, the addition of MSG+IMP increased the total taste intensity and percentage of participants who sensed umami. The addition of citric acid increased the salty taste intensity of 100 mM NaCl. The addition of citric acid also increased the total taste intensity, a greater percentage of participants discerned a sour taste. Furthermore, we observed the taste characteristics when adding lemon flavor, which evokes sourness, to the citric acid and NaCl mixture. Although the addition of lemon flavor did not affect the salty taste intensity, the number of participants who perceived a sour taste increased compared to those given only citric acid with the NaCl, and improvement in palatability was also observed. These results suggest that the addition of MSG+IMP and citric acid complicates the taste of NaCl solutions, and that they may enhance the salty taste.

Enhancing saltiness perception by chemosensory interaction: an fMRI study.

Neuroimaging studies that focus on taste, odor, and their interactions can specify their capability to elicit brain regions responsible for flavor perception and reward. Such information would be useful for formulating healthy food products, such as low salt food. In this study, a sensory experiment was conducted to investigate the capability of cheddar cheese odor, monosodium glutamate (MSG), and their interactions to enhance saltiness perception and preference of NaCl solutions. The activated brain areas in response to odor-taste-taste interactions were then investigated using an fMRI study. The results of the sensory tests showed that saltiness and preference of NaCl solutions were enhanced in the presence of MSG + cheddar cheese odor. According to the fMRI study, the stimulus with a higher salty rate activated the rolandic operculum, and the stimulus with a higher preference activated the rectus, medial orbitofrontal cortex, and substantia nigra. Moreover, the activation of multiple regions, such as the orbitofrontal cortex (OFC), anterior cingulate cortex (ACC), temporal pole, and amygdala was observed in response to (cheddar cheese odor + MSG + NaCl) minus (odorless air + NaCl).

Oral Exposure to Sodium Chloride without Subsequent Consumption Does Not Alter Salt Taste Function in Adults: A Cross-Over Intervention Study.

BACKGROUND: Reduction in dietary sodium increases salt taste sensitivity; however, non-oral sodium supplementation does not, suggesting that oral exposure is more important for modulating taste perception than consumption without tasting. OBJECTIVE: Using psychophysical methods, we assessed the effect of a two-week intervention involving oral exposure to a tastant without consumption on modulating taste function. METHODS: In a cross-over intervention study, n = 42 adults (age, mean ± SD: 29.7 ± 8.0 years) completed 4 intervention treatments requiring participants to rinse their mouths with 30 mL of a tastant, 3 times daily for 2 weeks. Treatments included oral exposure to 400 mM sodium chloride (NaCl), monosodium glutamate (MSG), monopotassium glutamate, and sucrose. Participants' taste function for salty, umami, and sweet [detection threshold (DT), recognition threshold (RT), and suprathreshold (ST)], and the glutamate-sodium discrimination status was evaluated before and after the tastant treatments. Effects of the interventions on taste function were assessed by using linear mixed models including treatment, time, and treatment x time interactions as fixed effects; significance was set at P > 0.05. RESULTS: There was no treatment × time interaction on DT and RT for all tastes assessed (P > 0.05). The only change in ST was following the NaCl intervention, participants' salt ST decreased at the highest concentration (400 mM) compared with the pre-NaCl treatment taste assessment (mean difference (MD): -0.052 [95% CI: -0.093, -0.010] labeled magnitude scale, P = 0.016). Compared with the pre-MSG treatment taste assessment, participants improved their ability to perform the glutamate-sodium discrimination task after the MSG intervention (MD:1.64 [95% CI: 0.395, 2.878] correct discrimination tasks, P = 0.010). CONCLUSION: Saltiness of an adult's free-living diet is unlikely to influence salt taste function, as oral exposure without consumption to a salt concentration greater than normally found in food, only attenuated taste responses to highly salty stimuli. This provides preliminary evidence that regulating salt taste function may require a coordinated response between oral activation and consumption of sodium.

Variaciones morfológicas de la glándula submandibular en ratas obesas por acción de glutamato monosódico / Morphological variations of the submandibular gland in obese rats by the action of monosodium glutamate

Este estudio tuvo como objetivo demostrar la existencia de variaciones morfológicas en el tejido conectivo de la glándula submandibular de ratas obesas expuestas a glutamato monosódico (GMS). Se utilizaron 12 ratas Sprague Dawley machos recién nacidas (6 ratas para el grupo 1, control; 6 ratas para el grupo 2 (GMS), 4 mg/g de glutamato monosódico de peso (5 dosis) mantenidas por 16 semanas respectivamente con una dieta y agua ad libitum. En el estudio se realizó un análisis estereológico e histológico, demostrándose una variación en el tejido conectivo presentando una disminución del volúmen glandular, mayor fibrosis, y disminución de adipocitos a nivel periférico siendo reemplazado por tejido rico en colágeno. Los vasos sanguíneos observados a nivel estereológico no presentan mayores cambios en cuanto a volumen, superficie y área.

SUMMARY: This study aims to demonstrate the existence of morphological variations in the connective tissue of the submandibular gland of obese rats exposed to MSG. Twelve male newborn Sprague Dawley rats were used (6 rats for group 1, control; 6 rats for group 2 (MSG), 4 mg/g of monosodium glutamate of weight (5 doses) maintained for 16 weeks respectively with a diet and water ad libitum. In the study, a stereological and histological analysis was carried out, demonstrating a variation in the connective tissue, presenting a decrease in the glandular volume, greater fibrosis, and a decrease in adipocytes at the peripheral level, being replaced by tissue rich in collagen. Blood cells observed at the stereological level do not present major changes in terms of volume, surface and area, but in the histological study greater vascularization is observed.

Enhanced preference for dried bonito dashi by prior experience with dashi and various taste substances in mice.

Dried bonito dashi, a complex mixture of sour, bitter, and umami substances as well as over 400 odorants, is the most widely used Japanese fish broth that enhances palatability of various dishes. Recent studies have suggested that prior experience with dried bonito dashi produces strong enhancement of subsequent intake and preference for dried bonito dashi. The present study investigated taste substances in dried bonito dashi that enhance subsequent dashi preference by its prior exposure. Male C57BL/6N mice were initially exposed for 10 days to (1) dried bonito dashi, (2) a chemical mixture of taste substances identified in dried bonito dashi (artificially reconstituted dashi), or (3) individual chemical solutions such as NaCl, monosodium l-glutamate (MSG), inosine 5'-monophosphate (IMP), lactic acid, histidine, and glucose. Intakes of 0.01-100% dried bonito dashi with water were then measured using ascending concentration series of 2-day two-bottle choice tests. Prior exposure to 1-100% dashi enhanced subsequent dashi preference in a concentration-dependent manner and the greatest effects were attained with 10-100% dashi exposure. Exposure to the reconstituted dashi also enhanced subsequent dashi preference. Among individual chemical solutions, 0.1% IMP produced modest enhancement of subsequent dashi preference, but neither NaCl, MSG, histidine, lactic acid, nor glucose did. These results suggest that IMP is at least a key substance that produces experience-based enhancement of dried bonito dashi preference.

Monosodium glutamate induces cortical oxidative, apoptotic, and inflammatory challenges in rats: the potential neuroprotective role of apigenin.

Monosodium glutamate (MSG) is used as a flavor, and a taste enhancer was reported to evoke marked neuronal impairments. This study investigated the neuroprotective ability of flavonoid apigenin against neural damage in MSG-administered rats. Adult male rats were allocated into four groups: control, apigenin (20 mg/kg b.wt, orally), MSG (4 g/kg b.wt, orally), and apigenin + MSG at the aforementioned doses for 30 days. Regarding the levels of neurotransmitters, our results revealed that apigenin augmented the activity of acetylcholinesterase (AChE) markedly, and levels of brain monoamines (dopamine, norepinephrine, and serotonin) accompanied by lessening the activity of monoamine oxidase (MAO) as compared to MSG treatment. Moreover, apigenin counteracted the MSG-mediated oxidative stress by decreasing the malondialdehyde (MDA) levels together with elevating the glutathione (GSH) levels. In addition, pretreatment with apigenin induced notable increases in the activities of cortical superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GR). Furthermore, apigenin attenuated the cortical inflammatory stress as indicated by lower levels of pro-inflammatory mediators such as interleukin-1 b (IL-1b), tumor necrosis factor-α (TNF-α), and nitric oxide (NO) as well as downregulated inducible nitric oxide synthase (iNOS) expression levels. Histopathological screening validated the abovementioned results and revealed that apigenin restored the distorted cytoarchitecture of the brain cortex. Thus, the present findings collectively suggest that apigenin exerted significant protection against MSG-induced neurotoxicity by enhancing the cellular antioxidant response and attenuating inflammatory machineries in the rat brain cortex.

The protective effect of L-carnitine on testosterone synthesis pathway, and spermatogenesis in monosodium glutamate-induced rats.

BACKGROUND: Monosodium glutamate (MSG) is a food ingredient that is increasingly used commercially. MSG leads to oxidative stress, consequently suppressing steroid hormone production that causes defects in male reproductive system. This study aimed to evaluate the effect of L-carnitine as an antioxidant on testicular damage in MSG-induced male rats. METHODS: Sixty adult male Spargue-Dawley rats were randomly divided into six groups of ten as follows: control (water), sham (normal saline), L-carnitine (200 mg/kg b.w), MSG (3 g/kg b.w), MSG + L-carnitine 100 (3 g/kg b.w of MSG and 100 mg/kg b.w of L-carnitine), and MSG + L-carnitine 200 (3 g/kg b.w of MSG and 200 mg/kg b.w of L-carnitine). The treatment was administered by oral gavage for six months. Serum levels of Malondialdehyde (MDA), Total Anti-oxidant Capacity (TAC), LH, FSH, testosterone, and mRNA expressions of Star, Cyp11a1, and Hsd17b3 genes, and histological and stereological changes were assessed. RESULTS: L-carnitine led to a significant decrease in the level of MDA and a significant rise in the serum levels of TAC, LH, FSH, and mRNA expression of Star and Cyp11a1 compared to the MSG group (p < 0.05). Furthermore, stereological results indicated a significant increment in the number of sexual lineage cells, the total volume of the testis, length, diameter, and volume of seminiferous tubules, the height of the germinal epithelium, sperm count, and sperm motility (p < 0.05) in MSG + L-carnitine 200 compare to MSG group. CONCLUSION: The study's findings demonstrated that L-carnitine due to its anti-oxidant properties, ameliorated the reproductive abnormalities in the male rats exposed to MSG.

Comment on Nahok et al. Monosodium Glutamate Induces Changes in Hepatic and Renal Metabolic Profiles and Gut Microbiome of Wistar Rats. Nutrients 2021, 13, 1865.

This letter is to comment on the study of Nahok, K. et al. [...].

Reply to Chao et al. Comment on "Nahok et al. Monosodium Glutamate Induces Changes in Hepatic and Renal Metabolic Profiles and Gut Microbiome of Wistar Rats. Nutrients 2021, 13, 1865".

We sincerely appreciate the thorough review and insights of Dr. Huichia Chao and colleagues [...].

Investigating the Influence of Different Umami Tastants on Brain Perception via Scalp Electroencephalogram.

Three types of tastants are known as perceptually associated with umami taste: monosodium glutamate (MSG), disodium succinate (WSA), and disodium inosine monophosphate (IMP). While these tastants were confirmed to be perceptually similar in a sensory study, they could be discriminated (p < 0.05) by electroencephalogram (EEG) analysis on a time scale of 5-6 s. In comparison of the EEG responses of the participants, the brain could partly distinguish (p < 0.05) between different sensory intensities of MSG, WSA, or IMP. The EEG data indicated that the brain is partially sensitive to perceiving different sensory intensities (L, low; M, medium; and H, high) of the same umami stimuli; i.e., for MSG in µV2/Hz, L, 2.473 ± 0.181; M, 3.274 ± 0.181; and H, 3.202 ± 0.181. However, brain responses of perceptually equi-umami intensities could partially be discriminated, suggesting that the brain could partially discriminate (p < 0.05) MSG, WSA, and IMP, despite similar sensory intensities. Moreover, umami tastants were also found to significantly enhance (p < 0.05) the α wave activity, with the most responsive being at 10 Hz, particularly in the frontal and parietal and occipital regions of the brain (p < 0.001). This study shows the potential of EEG to investigate brain activity triggered by umami stimuli.

Vasoactive intestinal peptide promotes hypophagia and metabolic changes: Role of paraventricular hypothalamic nucleus and nitric oxide.

Vasoactive intestinal peptide (VIP), a neuromodulator present in the hypothalamus, plays an important role in the regulation of food intake. Paraventricular nucleus of the hypothalamus (PVN) is involved in ingestive responses and regulates the nitric oxide (NO) pathway. The main objectives of this study were to investigate metabolic changes established after different doses and times of VIP microinjection on the PVN, and the effect of VIP microinjection on the PVN on food intake and the role of NO in this control. In anesthetized rats, increased blood plasma glucose and insulin levels were observed following the doses of 40 and 80 ng/g of body weight. At the dose of 40 ng/g, VIP promoted hyperglycemia and hyperinsulinemia 5, 10, and 30 min after microinjection, and increased free fatty acids and total lipids plasma levels after 5 min, and triglycerides after 10 min. In awake animals, once again, VIP administration increased plasmatic levels of glucose, free fatty acids, corticosterone, and insulin 10 min after the microinjection. Moreover, VIP promoted hypophagia in the morning and night periods, and L-arginine (L-Arg) and monosodium glutamate (MSG) or a combination of both attenuated VIP-induced reduction on food intake. In addition, nitrate concentration in the PVN was decreased after VIP microinjection. Our data show that the PVN participates in the anorexigenic and metabolic effects of VIP, and that VIP-induced hypophagia is likely mediated by reduction of NO.

THE FEATURES OF THE NORMAL ULTRASTRUCTURE OF THE RAT DUODENUM AND UNDER THE COMBINED EFFECT OF THE FOOD ADDITIVES COMPLEX.

OBJECTIVE: The aim: Investigation of ultrastructural changes in the elements of rats' duodenal mucosa in norm and exposed to a complex of food additives (monosodium glutamate, sodium nitrite and Ponceau 4R). PATIENTS AND METHODS: Materials and methods: 70 rats of the experimental groups was administered 0.6 mg/kg of sodium nitrite, monosodium glutamate at a dose of 20 mg/kg, Ponceau 4R at a dose of 5 mg/kg in 0.5 ml of distilled water once daily per os. The doses of food additives were twice lower the allowable normal rate in food products. Animals were removed from the experiment at 1, 4, 8, 12 and 16 weeks. RESULTS: Results: The effect of the complex of food additives on the mucous membrane of the duodenum was manifested by the development of edema and increased local immune response. In the later stages of observation, dystrophic changes in epithelial cells were determined. Vacuoles were found in the cytoplasm. CONCLUSION: Conclusions: The use of a complex of food additives led to general ultramicroscopic changes in the mucous membrane of rats' duodenum, triggering the morphological mechanisms of nonspecific inflammation in the form of dystrophic changes and the development of apoptosis.

MORPHOLOGICAL FEATURES OF THE LIVER PARENCHYMA IN THE EXPERIMENTAL SUPPLEMENTATION OF RATION WITH THE FOOD ADDITIVES.

OBJECTIVE: The aim: The aim of the paper was the experimental study of the morphological features of albino rat hepatocytes after the consumption of the complex of food additives (monosodium glutamate, sodium nitrite, Ponceau 4R) supplemented into the ration and consumed for four weeks. PATIENTS AND METHODS: Materials and methods: The study was performed on 30 outbred albino rats of both genders, weighing 204±0.67 g. The ration of the experimental animals, supplemented with a combination of food additives, namely, monosodium glutamate, Ponceau 4R, sodium nitrate, was consumed for 1 and 4 weeks. The study of the structure of hepathocytes was carried out on traditional histological preparations and preparations stained with Best's carmine. RESULTS: Results: Supplementation of ration with the complex of food additives for one week showed the phenomena of fatty degeneration that dominated in hepatocytes, and in a longer consumption of food additives in the ration (for four weeks), the number of liver cells with the phenomena of hydropic degeneration significantly increased, while individual hepatocytes had signs of irreversible destructive changes. CONCLUSION: Conclusions: Consumption of the complex of food additives supplemented into the standard ration of laboratory animals for 4 weeks leads to a significant change in the dimensions of the liver cells, a decrease in their glycogen content, and a progressive increase in the number of hepatocytes with alterations.

Further disentangling the motivational processes underlying benzodiazepine hyperphagia.

In addition to their well-known anxiolytic functions, benzodiazepines produce hyperphagia. Previously, we reported that the benzodiazepine, chlordiazepoxide (CDP), increased consumption of both normally-preferred and normally-avoided taste stimuli during long-term (1 h) tests, primarily through changes in licking microstructure patterns associated with hedonic taste evaluation, whereas there was little effect on licking microstructure measures associated with post-ingestive feedback. In this study, we further examined the hedonic and motivational specificity of CDP effects on ingestive behavior. We tested brief access (15 s) licking responses for tastants spanning all taste qualities after treatment with either CDP (5 or 10 mg/kg) or the non-benzodiazepine anxiolytic, buspirone (1.5 or 3 mg/kg). A between-subjects, counterbalanced design compared the CDP or buspirone effects on licking responses for water and a range of weak to strong concentrations of NaCl, Q-HCl, citric acid, MSG, saccharin, and capsaicin under water-restricted (23 h) conditions; and sucrose, saccharin, and MSG under water-replete conditions. In a dose dependent manner, CDP increased licking for taste stimuli that were normally-avoided after saline treatment, with a notable exception observed for the trigeminal stimulus, capsaicin, which was not affected at any concentration or drug dose, suggesting a taste-specific effect of CDP on orosensory processing. Under water-replete conditions, CDP dose-dependently increased licking to normally-accepted concentrations of sucrose, saccharin, and MSG. There was no effect of either drug on licks for water under either water-restricted or water-replete conditions. Buspirone slowed oromotor coordination by increasing brief interlick intervals, but it did not affect licking for any concentrations of the tastants. Overall, these results indicate that benzodiazepines selectively enhance the hedonic acceptance of gustatory orosensory stimuli, independent of general anxiolytic or oromotor coordination effects, or physiological states such as thirst.

Apocynin reduces cytotoxic effects of monosodium glutamate in the brain: A spectroscopic, oxidative load, and machine learning study.

Herein, we examined the modulatory effects ofApocynum (APO) on Monosodium Glutamate (MSG)-induced oxidative damage on the brain tissue of rats after long-term consumption of blood serum components by biochemical assays, Fourier transform infrared spectroscopy(FTIR), and machine learning methods. Sprague-Dawley male rats were randomly divided into the Control, Control + APO, MSG, and MSG + APO groups (n = 8 per group). All administrations were made by oral gavage saline, MSG, or APO and they were repeated for 28 days of the experiments. Brain tissue and blood serum samples were collected and analyzed for measurement levels ofmalondialdehyde (MDA),glutathione (GSH),myeloperoxidase (MPO), superoxide dismutase (SOD) activity, and Spectroscopic analysis. After 29 days, the results were evaluated using machine learning (ML). The levels of MDA and MPO showed changes in the MSG and MSG + APO groups, respectively. Changes in the proteins and lipids were observed in the FTIR spectra of the MSG groups. Additionally, APO in these animals improved the FTIR spectra to be similar to those in the Control group. The accuracy of the FTIR results calculated by ML was 100%. The findings of this study demonstrate that Apocynin treatment protectsagainst MSG-induced oxidative damage by inhibitingreactive oxygen speciesand upregulatingantioxidant capacity, indicating its potential in alleviatingthe toxic effects of MSG.