Neonatal Administration Of Monosodium Glutamate Research Articles

Exercise and Vitamin D Supplementation Modify Spleen Morphology in Lean, but not, in Monosodium-Glutamate-Obese Rats

We evaluated the effect of exercise and vitamin D supplementation on histological aspects of the spleens of lean and obese rats. Male Wistar rats received neonatal administration of monosodium glutamate (MSG; 4g/Kg), while Control (CON) rats received an equimolar solution. At 30 days of age, CON and MSG rats were subdivided into Exercised (E) or Sedentary (S) groups and Vitamin D (VD; 12µg/Kg) supplemented or non-supplemented (NS) groups. At the 86th day of life, rats were euthanized, and their body weights and adiposity were evaluated. Spleens were submitted to histomorphometric analysis of the white pulp (WP), germinal center (GC) and lymphatic nodule (LN). Data are presented as mean ± SEM (p<0.05). MSG treatment promoted a reduction in spleen weight, increased LN thickness and WP area, but reduced GC occupation, compared to spleens of CON-lean rats (p<0.05). Exercise and VD did not provoke changes in the spleens of MSG-obese rats. In CON-lean rats, E and VD induced augmentation of LN thickness. VD supplementation increased the WP area, while E reduced GC area occupation in spleens of CON-lean rats (p<0.05). In conclusion, exercise and VD supplementation increased LN thickness and WP area, but had the opposite effect on the GC in spleens of CON-lean rats. However, neither exercise nor VD supplementation prevented the development of morphological abnormalities in the spleens of MSG-obese rats.

Neonatal Monosodium Glutamate Administration Disrupts Place Learning and Alters Hippocampal–Prefrontal Learning-Related Theta Activity in the Adult Rat

Neonatal treatment with monosodium glutamate causes profound deficits in place learning and memory in adult rats evaluated in the Morris maze. Theta activity has been related to hippocampal learning, and increased high-frequency theta activity occurs through efficient place learning training in the Morris maze. We wondered whether the place learning deficits observed in adult rats that had been neonatally treated with monosodium glutamate (MSG), were related to altered theta patterns in the hippocampus and prelimbic cortex, which were recorded during place learning training in the Morris maze. The MSG-treated group had a profound deficit in place learning ability, with a marginal reduction in escape latencies during the final days of training. Learning-related changes were observed in the relative power distribution in control and MSG-treated groups in the hippocampal EEG, but not in the prelimbic cortex. Increased prefrontal and reduced hippocampal absolute power that appeared principally during the final days of training, and reduced coherence between regions throughout the training (4–12 Hz), were observed in the MSG-treated rats, thereby suggesting a misfunction of the circuits rather than a hyperexcitable general state. In conclusion, neonatal administration of MSG, which caused a profound deficit in place learning at the adult age, also altered the theta pattern both in the hippocampus and prelimbic cortex.

Monosodium glutamate induced nociception and oxidative stress dependent on time of administration, age of rats and susceptibility of spinal cord and brain regions

Monosodium glutamate (MSG), a food flavor enhancer used worldwide, has been studied because it may cause neurotoxicity, which is associated with oxidative stress. The aim of this study was to investigate whether spinal cord and brain regions are affected by oxidative stress and the temporal profile of nociceptive responses induced by MSG in newborn and adult rats. The newborn (post natal day, PND 1) Wistar rats received ten subcutaneous injections of MSG (4.0 g/kg) or saline solution. At PND 3, 11 or 90, the rats performed nociceptive tests and parameters of oxidative stress were evaluated in samples of spinal cord and brain regions. Adult rats (PND 90) were injected with MSG (4.0 g/kg, 10 injections) or saline solution, but MSG did not induce nociception or oxidative stress. The neonatal administration of MSG increased nociceptive behavior in the tail immersion, hot plate and formalin tests and decreased the SOD activity in spinal cord of PND 3 rats. In rats at PND 11 and 90, the neonatal administration of MSG increased mechanical allodynia and nociceptive behavior in the hot plate and formalin tests. The neonatal administration of MSG induced oxidative stress in the hippocampus of rats at PND 11 and in the cerebral cortex at PND 90. These findings demonstrate that nociception and oxidative stress was induced in rats dependent on the time of MSG administration, susceptibility of spinal cord and brain regions and the age of rats.

Probiotic strains of lactobacilli and bifidobacteria alter pro- and anti-inflammatory cytokines production in rats with monosodium glutamate-induced obesity.

The aim of this study was to investigate the effect of probiotic strains of Lactobacillus casei IMV B-7280, Bifidobacterium animalis VKL, B. animalis VKB on the pro- and anti-inflammatory cytokines production in Wistar male rats with monosodium glutamate (MSG)-induced obesity. It was established that neonatal administration of MSG to rats leads to increasing levels of the interleukin (IL)-1β and IL-12, and to decreasing ofthe IL-4, IL-10 and tumor growthfactor (TGF)-β levels in the bloodserum. After administration of the B. animalis VKL - B. animalis VKB - L. casei IMV B-7280 composition to obese rats the level of the IL-lP in blood serum wasn't differ from that in the obese rats, that didn't receive of the probiotic bacteria. But there was no statistically signifcant difference comparing with intact rats. The level of the IL-12B p4O in blood serum was decreased under influence of the B. animalis VKL - B. animalis VKB - L. casei IMV B-7280 composition (18.9%, p < 0.05) and B. animalis VKL (10.5%, p < 0.05) compared with obese rats, not receiving probiotic bacteria, but remained higher than in intact animals. After administration to obese rats ofthe B. animalis VKL - B. animalis VKB - L. casei IMV B-7280 composition the levels ofthe IL-4, IL- 10 and TGF-β increased in blood serum comparing with obese rats, not receiving probiotic bacteria. The level of the IL-10 also increased under influence of the B. animalis VKB, and IL-4 - under influence of the L. casei IMVB-7280. Our results suggest that these probiotic bacteria and probiotic composition are able to down-regulation the inflammation in rats with MSG-induced obesity but the strongest anti-inflammatory effects have probiotic composition. The ability of lactobacilli and bifdobacteria to alter the pro- and anti-inflammatory cytokines production, opens perspectives to create new treatments for obesity and metabolic syndrome based on probiotics.

Pathophysiology characteristics of the experimental model of obesity in female rats induced neonatal administration of monosodium glutamate

It was shown that in rats of 4 months age, the injection of monosodium glutamate elicited visceral obesity. To confirm the symptoms of obesity with type 2 diabetes, we had a glucose-tolerant test. In animals with obesityб glucose levels in 2 hours after a glucose was 10,65±2,215mmol / L, that was noted glucose intolerance

Dose-related antihyperglycemic and hypolipidemic effects of two novel thiazolidin-4-ones in a rodent model of metabolic syndrome.

The replacement of the thiazolidinedione moiety with a thiazolidinone may yield antidiabetic compounds with similar pleiotropic effects. Hence, the aim of the present study was to explore the dose-related antihyperglycemic and hypolipidemic effects of two synthesized novel thiazolidin-4-one derivatives, one with a nicotinamide and the other with a p-chlorophenoxyacetamide substitution at the N3 position of the thiazolidinone ring (NAT1 and PAT1, respectively), in a rodent model of metabolic syndrome (MetS). Metabolic syndrome was induced in Wistar rats by neonatal administration of monosodium glutamate (i.p.) on 4 consecutive days followed by high-sucrose diet feeding for 6 months. The effects of NAT1 (33 and 66 mg/kg) and molar equivalent doses of PAT1 (40 and 80 mg/kg) on relevant biochemical parameters were evaluated. Because MetS is a state of chronic low-grade inflammation, we also evaluated the effects of these compounds on proinflammatory markers, namely interleukin (IL)-6, tumor necrosis factor (TNF)-α, reactive oxygen species (ROS), and nitric oxide (NO). Both NAT1 and PAT1 attenuated hyperglycemia, hypertriglyceridemia, hypoalphalipoproteinemia, and glucose intolerance. PAT1 exhibited superior antihyperglycemic and antihypoalphalipoproteinemic effects than NAT1. However, NAT1 had a better triglyceride-lowering effect. At the lower dose tested, both compounds significantly reduced elevated malondialdehyde levels. In addition, PAT1 (80 mg/kg) restored hepatic superoxide dismutase enzyme levels. There was a tendency for NAT1 and PAT1 to inhibit elevated hepatic IL-6 and TNF-α levels, but the differences did not reach statistical significance. In addition, PAT1 exhibited in vitro anti-inflammatory activity by reducing proinflammatory ROS and NO levels in RAW264.7 macrophages. The novel thiazolidin-4-ones NAT1 and PAT1 could be potential pleiotropic drug candidates targeting MetS.

Antinociceptive action of diphenyl diselenide in the nociception induced by neonatal administration of monosodium glutamate in rats

Monosodium glutamate (MSG) is a neuroexcitatory amino acid commonly used as flavoring of foods. MSG neonatal administration to animals leads to behavioral and physiological disorders in adulthood, including increased pain sensitivity. This study aimed to investigate the effect of diphenyl diselenide (PhSe)2, an organoselenium compound with pharmacological properties already documented, on nociception induced by MSG. Newborn Wistar rats received 10 subcutaneous injections of MSG at a dose of 4.0g/kg or saline (once daily). At the 60th day of life, the rats were daily treated with (PhSe)2 (1mg/kg) or vehicle (canola oil) by the intragastric route for 7 days. The behavioral tests (locomotor activity, hot plate, tail-immersion and mechanical allodynia) were carried out. Ex vivo assays were performed in samples of hippocampus to determine Na+, K+-ATPase and Ca2+-ATPase activities, cytokine levels and [3H]glutamate uptake. The results demonstrated that MSG increased nociception in the hot plate test and in the mechanical allodynia stimulated by Von-Frey hair but did not alter the tail immersion test. (PhSe)2 reversed all nociceptive behaviors altered by MSG. MSG caused an increase in Na+,K+-ATPase and Ca2+-ATPase activities and in pro-inflammatory cytokine levels and a decrease in the anti-inflammatory cytokine and in the [3H]glutamate uptake. (PhSe)2 was effective in reversing all alterations caused by MSG. The results indicate that (PhSe)2 had a potential antinociceptive and anti-inflammatory action in the MSG model.

Параметри вуглеводного обміну при глутамат-індукованому ожирінні у щурів за умов корекції пробіотичними штамами лактобацил та біфідобактерій

To find out the effect of probiotic strains on insulin resistance induced by glutamate-induced obesity in rats. Obesity was induced by neonatal administration of monosodium glutamate (4 mg/g,s.c.) at 2, 4, 6, 8, 10-day life. The introduction of probiotics started at the end of 4 week after birth and continued intermittently for 2-week courses. After 4 months, the rats of all groups glucose and insulin levels and insulin resistance index HOMA were analyzed. Neonatal administration of monosodium glutamate leads to the development of insulin resistance in rats 4 months of age. The periodic introduction of the combined probiotics prevented the development insulin resistance in rats. The most significant effect was revealed in the group of animals treated with the combined probiotic strains Lactobacillus casei IMVB-7280, Bifidobacterium animalis VKL, Bifidobacterium animalis VKB. The results suggest the effectiveness of the use of probiotic strains of bifidobacteria and to prevent the development of insulin resistance.

Розвиток експериментального ожиріння у щурів, викликаного дією глутамату натрію, на тлі введення пробіотиків

The effect of a mixture of probiotic strains (2:1:1 Lactobacillus casei IMVB-7280, Bifidobacterium animalis VKL, Bifidobacterium animalis VKB) on the development of experimental obesity in rats induced by neonatal administration of monosodium glutamate has been studied. It was shown that in rats of 4 months age, the injection of monosodium glutamate (4 mg/g) at 2, 4, 6, 8, 10 days after birth elicited abdominal obesity and metabolic syndrome. An intermittent administration of a probiotic mixture to rats treated with monosodium prevented the development of obesity. In the group of rats treated with probiotics, anthropometric parameters (weight and body length, Lee index, body mass index) did not differ from the level of intact rats. Visceral fat mass was decreased by probiotics by 38.5% (P < 0.05) compared to rats treated with water. Probiotics improved lipid metabolism: reduced the level of VLDL by 32.2% (P < 0,05), the level of LDL by 30.6% (P < 0.05), increased HDL by 25.7% (P <0,05) compared to obese control rats. Probiotic strains restored the secretion of adipocytes hormones (leptin and adiponectin) to the normal level of intact animals. The results show the effectiveness of probiotics for the prevention of obesity.

Swim training restores glucagon-like peptide-1 insulinotropic action in pancreatic islets from monosodium glutamate-obese rats

Glucagon-like peptide-1 (GLP-1) is an important modulator of insulin secretion by endocrine pancreas. In the present study, we investigated the effect of swim training on GLP-1 insulinotropic action in pancreatic islets from monosodium glutamate (MSG)-obese rats. Obesity was induced by neonatal MSG administration. MSG-obese and control (CON) exercised rats swam for 30 min (3 times week(-1) ) for 10 weeks. Pancreatic islets were isolated by colagenase technique and incubated with low (5.6 mM) or high (16.7 mM) glucose concentrations in the presence or absence of GLP-1 (10 nM). In addition, GLP-1 gene expression in ileum was quantified in fasting and glucose conditions. Exercise reduced obesity and hyperinsulinemia in MSG-obese rats. Swim training also inhibited glucose-induced insulin secretion in islets from both groups. Islets from MSG-obese rats maintained GLP-1 insulinotropic response in low glucose concentration. In contrast, in the presence of high glucose concentration, GLP-1 insulinotropic action was absent in islets from MSG-obese rats. Islets from MSG-exercised rats showed reduced GLP-1 insulinotropic action in the presence of low glucose. However, in high glucose concentration swim training restored GLP-1 insulinotropic response in islets from MSG-obese rats. In all groups, glucose intake increased GLP-1 immunoreactivity and gene expression in ileum cells in relation to fasting conditions. Swim training reduced these parameters only in ileum cells from CON-exercised rats. Neither MSG treatment nor exercise affected GLP-1 expression in the ileum. Exercise avoids insulin hypersecretion restoring GLP-1's insulinotropic action in pancreatic islets from MSG-obese rats.

Renal sympathetic nerve activity is increased in monosodium glutamate induced hyperadipose rats

The literature suggests that both obesity and hypertension are associated with increased sympathetic nerve activity. In the present study we evaluated the renal sympathetic nerve activity (RSNA), mean arterial pressure (MAP) and heart rate (HR) in hyperadipose rats induced by neonatal administration of monosodium glutamate (MSG). Neonatal Wistar male rats were injected with MSG (4mg/g body weight ID) or equimolar saline (control) for 5 days. At 90th day, all rats were anesthetized (urethane 1.4g/kg) and prepared for MAP, HR and renal sympathetic nerve activity recordings. The anesthetized MSG rats presented baseline hypertension and increased baseline RSNA compared with control. Our results suggest the involvement of the renal sympathetic nervous system in the physiopathology of the MSG obesity.

Pentamethylquercetin generates beneficial effects in monosodium glutamate-induced obese mice and C2C12 myotubes by activating AMP-activated protein kinase

Pentamethylquercetin (PMQ) has recently been shown to have glucose-lowering properties. Here, we aimed to characterise the effectiveness and underlying mechanisms of PMQ for ameliorating metabolic disorders in vivo and vitro. We generated a mouse model of obesity by neonatal administration of monosodium glutamate (MSG) and used it to assess the properties of PMQ as a treatment for metabolic disorders. We also investigated the possible underlying mechanisms of PMQ in the prevention of metabolic disorders. Compared with normal mice, MSG mice had metabolic disorders, including central obesity, hyperinsulinaemia, insulin resistance, hyperglycaemia, hyperlipidaemia, decreased phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC), and downregulated levels of GLUT4 in gastrocnemius muscles. In MSG mice, PMQ treatment (5, 10, 20 mg/kg daily) reduced body weight gain, waist circumference, adipose tissue mass, serum glucose, triacylglycerol and total cholesterol, while improving insulin resistance, activating AMPK and increasing ACC phosphorylation and GLUT4 abundance. In C2C12 myotubes, PMQ (10 μmol/l) increased glucose consumption by ∼65%. PMQ treatment (1-10 μmol/l) also activated AMPK, increased ACC phosphorylation and GLUT4 abundance, and upregulated the expression of some key genes involved in fatty acid oxidation. These findings suggest that PMQ can ameliorate metabolic disorders at least in part via stimulation of AMPK activity.

Disappearance of sexual dimorphism in triptolide metabolism in monosodium glutamate treated neonatal rats

Triptolide (CAS 38748-32-2), a major active component of Tripterygium wilfordii Hook F (TWHF), was reported to be sex-dependently metabolized mainly due to sex-related expression of CYP3A2. Sexual dimorphism in the expression of CYP isoforms is affected by sex difference in daily rhythm of growth hormone (GH) secretion. Neonatal administration of monosodium glutamate (MSG) can produce latent developmental defects in GH secretion and associated sex-dependent hepatic enzymes. In the present study, the triptolide metabolism, CYP3A2 expression and CYP3A-dependent activity were evaluated in Sprague-Dawley rats treated neonatally with MSG (4 mg/g) or saline (control) on postnatal days 1, 3, 5, 7 and 9. Treatment with MSG during the neonatal period in both sexes caused a number of disorders characterized by stunted body growth, notable obesity and suppression of GH secretion to barely detectable levels. In addition, neonatal treatment with MSG nearly eliminated the male-specific CYP3A2 expression and significantly reduced the microsomal erythromycin N-demethylation activity in males, while having no effects on CYP3A2 protein in females. Consistent with the P450 findings, the sexual dimorphism of triptolide metabolism completely disappeared in MSG-treated rats. This suggested that neonatal MSG treatment could eliminate the sex-dependent difference in metabolism of triptolide by suppressing CYP3A2 expression and activity in males to the same extent as females.

Effect of Food Restriction on Energy Expenditure of Monosodium Glutamate-Induced Obese Rats

The neonatal administration of monosodium glutamate (MSG) to rodents leads to obesity in the adult animal, characterized by increased fat storages. Chronic food restriction is known to induce reduction in body energy expenditure, as an adaptive mechanism to save energy. Our purpose was to examine whether obesity can alter the mechanism of energy conservation in food-restricted animals. Newborn female Wistar rats were injected either MSG (obese) or saline (control). At the age of 90 days, the animals were fed daily ad libitum (control and MSG) or restricted (50%) (control-restricted and MSG-restricted). After 30 days the animals were sacrificed and the energy balance was determined by calorimetric analysis. Some parameters of energy balance and body composition were affected by MSG treatment as well as food restriction. The percent reduction of the energy expenditure and fat content in MSG-restricted animals was lower than control-restricted animals, when compared with their respective ad libitum groups. These results indicate that all food-restricted animals were able to develop the mechanism of energy conservation, regardless of the obesity, but it was less efficient in MSG-obese animals.

Effects of the neonatal treatment with monosodium glutamate on myenteric neurons and the intestine wall in the ileum of rats

The neonatal administration of a 4 mg/g dose of monosodium glutamate (MSG) to rodents leads to neuronal death in the hypothalamus arcuate nucleus, which leads in turn to obesity in the adult animal. However, few studies have investigated the effects on the enteric nervous system. This study evaluated the effects of the neonatal administration of MSG on the frequency and morphometry of the myenteric as well as the ileum wall morphometry of adult Wistar male rats. Whole-mount preparations of ileum samples were stained by the Giemsa or NADH-diaphorase histochemical methods. For histological processing, hematoxylin and eosin staining was used. The treatment with MSG led to obesity, as shown by the higher values for Lee's index and the weights of periepididimal and retroperitoneal adipose tissues. The Giemsa staining revealed a significantly larger neuronal density in the MSG group, which is explained by smaller physical growth and a reduction in the weight of the small intestine. The mean neuronal profile did not change between groups. The NADH-diaphorase-positive neuronal subpopulation kept its neuronal density but its average cellular profile was reduced in the MSG group. A morphometric analysis of the intestinal wall, muscular layer, villi, and intestinal crypts showed that their characteristics did not change. The treatment with MSG did not cause alteration of the total myenteric population of the ileum, but it influenced the NADH-diaphorase-positive subpopulation. From the maintenance of the morphometric parameters of the ileum intestinal wall, we inferred that intestinal function was preserved in obese animals.

Relationship between Pituitary and Adipose Tissue after Hypothalamic Denervation in the Female Rat

Neonatal administration of monosodium glutamate (MSG) to rats produces severe lesions in certain hypothalamic nuclei, with repercussions in different neuroendocrine axes, and serves as a model for their study. In addition, adipose tissue, as a target organ, is known to be directly related to several neurondocrine axes. We used 21-day-old female Sprague-Dawley rats that had received a neonatal treatment with MSG (4 mg/g body weight, i.p., from day 2 up to day 10 of age) in addition to control rats (injected with 10% NaCl solution, on a similar schedule). We performed a specific immunohistochemical study on each anterior-pituitary cell population, along with the morphometry of these cells and of the parietal and visceral adipose tissue, and measured the levels of serum leptin and triglycerides. The MSG animals evinced significant changes in volume density (VD), cell density (CD), and cell size (CS) in the corticotropes, thyrotropes, and LH gonadotropes, but not in the somatotropes, lactotropes, and FSH gonadotropes. The modification common to the three cell types was a hyperplasia, but with different results depending on cell size. Furthermore, in the MSG rats significant changes were also observed in the VD, CD, and CS of the adipose tissue, consisting of adipogenesis and decrease of adipocyte size in visceral fat, together with probable lipogenesis as judged by an increase in adipocyte size in the parietal fat. The serum levels of leptin and triglycerides appeared significantly higher in MSG animals. For the first time in this animal model, and at the level of three neuroendocrine axes, our results suggest changes that correlate hypothalamic damage, cellular pituitary alterations, and the response of the adipose tissue as a target organ for MSG insult.

Role of premature leptin surge in obesity resulting from intrauterine undernutrition

Intrauterine undernutrition is closely associated with obesity related to detrimental metabolic sequelae in adulthood. We report a mouse model in which offspring with fetal undernutrition (UN offspring), when fed a high-fat diet (HFD), develop pronounced weight gain and adiposity. In the neonatal period, UN offspring exhibited a premature onset of neonatal leptin surge compared to offspring with intrauterine normal nutrition (NN offspring). Unexpectedly, premature leptin surge generated in NN offspring by exogenous leptin administration led to accelerated weight gain with an HFD. Both UN offspring and neonatally leptin-treated NN offspring exhibited an impaired response to acute peripheral leptin administration on a regular chow diet (RCD) with impaired leptin transport to the brain as well as an increased density of hypothalamic nerve terminals. The present study suggests that the premature leptin surge alters energy regulation by the hypothalamus and contributes to "developmental origins of health and disease."

Neonatal administration of monosodium glutamate prevents the development of ethanol- but not psychostimulant-induced sensitization: a putative role of the arcuate nucleus.

Lesions of the arcuate nucleus by monosodium glutamate, goldthioglucose and oestradiol valerate treatments are known to prevent the acute stimulating effect of ethanol in mice. On the basis of these results, the current study analysed whether a lesion of the arcuate nucleus by monosodium glutamate was able to block ethanol-induced locomotor sensitization. To produce the arcuate nucleus lesions, pups were injected with saline or monosodium glutamate (4 mg/g body weight) subcutaneously on 5 alternate days, starting on postnatal day one. Sensitization treatments began 10 weeks after the initial lesions. Sensitization training consisted of six trials on alternate days, in which groups of mice were treated with ethanol (2 g/kg) or saline, and then tested in an open-field for the induction of locomotor activity. The present study demonstrated that animals with monosodium glutamate-induced lesions did not develop locomotor sensitization to ethanol. Different groups of mice were used to assay blood ethanol levels and to evaluate the effect of arcuate nucleus lesions on psychostimulant-induced locomotor sensitization. Sensitization to cocaine or amphetamine was spared in monosodium glutamate-pre-treated animals, although the lesion of arcuate nucleus reduced the sensitivity of mice to cocaine. Our findings therefore suggest that the arcuate nucleus may be critical for the neuroadaptations that underlie the behavioural sensitization to ethanol, in contrast to those mediating psychostimulant-induced sensitization.

Neuroendocrine alterations impair enamel mineralization, tooth eruption and saliva in rats.

Neonatal administration of monosodium glutamate (MSG) in rats causes definite neuroendocrine disturbances which lead to alterations in many organ systems. The possibility that MSG could affect tooth and salivary gland physiology was examined in this paper. Male and female pups were injected subcutaneously with MSG (4 mg/g BW) once a day at the 2nd, 4th, 6th, 8th and 10th day after birth. Control animals were injected with saline, following the same schedule. Lower incisor eruption was determined between the 4th and the 10th postnatal days, and the eruption rate was measured between the 43rd and the 67th days of age. Pilocarpine-stimulated salivary flow was measured at 3 months of age; protein and amylase contents were thereby determined. The animals treated with MSG showed significant reductions in the salivary flow (males, -27%; females, -40%) and in the weight of submandibular glands (about -12%). Body weight reduction was only about 7% for males, and did not vary in females. Saliva of MSG-treated rats had increased concentrations of total proteins and amylase activity. The eruption of lower incisors occurred earlier in MSG-treated rats than in the control group, but on the other hand the eruption rate was significantly slowed down. The incisor microhardness was found to be lower than that of control rats. Our results show that neonatal MSG treatment causes well-defined oral disturbances in adulthood in rats, including salivary flow reduction, which coexisted with unaltered protein synthesis, and disturbances of dental mineralization and eruption. These data support the view that some MSG-sensitive hypothalamic nuclei have an important modulatory effect on the factors which determine caries susceptibility.

Prevention of latently expressed CYP2C11, CYP3A2, and growth hormone defects in neonatally monosodium glutamate-treated male rats by the N-methyl-D-aspartate receptor antagonist dizocilpine maleate.

Neonatal administration of monosodium glutamate (MSG) can produce latently expressed defects in drug metabolism and growth hormone secretion as well as stunted growth and obesity. Instead of secreting growth hormone in the masculine episodic profile, plasma hormone levels are generally undetectable in affected adult male rats. Moreover, male-specific isoforms of cytochrome P450 (P450; e.g., CYP2C11 and CYP3A2), whose combined levels comprise the bulk of the total hepatic P450 in adult male rats, are similarly undetectable in these animals. Since "signaling elements" in the masculine episodic growth hormone profile are solely responsible for the elevated characteristic male-like expression levels of CYP2C11 and CYP3A2, suppression of the isoforms in the MSG-treated rats appeared to be caused by the simple absence of the hormone from the circulation. However, the reported failures of restored physiologic masculine growth hormone profiles to correct the P450 defects suggested the occurrence of direct MSG-induced liver damage independent of the well known hypothalamic lesions produced by the amino acid. Concurrent administration of dizocilpine maleate (MK-801), a selective and highly potent noncompetitive N-methyl-D-aspartate receptor antagonist of glutamate, completely prevented the adverse effects of neonatal MSG treatment on P450 expression, growth hormone secretion, and growth parameters, indicating that the amino acid-induced defects are solely a result of neuronal (i.e., hypothalamic) damage produced at the time of MSG exposure. The irreversibility of the P450 damage is described as resulting from secondary defects initially induced by the neuronal lesions.