Introduction

Monosodium glutamate (MSG), a principal constituent of natural protein-rich food (Freeman 2006) and a sodium salt of L-glutamic acid, is used widely as a flavour enhancer of meats, snacks, seafood, stews, and soups. MSG has been implicated in several neurological impairments via glutamate excitotoxicity (Eweka et al. 2011). MSG uses glutamate receptors, which include ionotropic glutamate receptors such as NMDA, AMPA, and kainite receptors, and the metabotropic glutamate receptors (mGluRs) for the excitatory neurotransmitter glutamate (Hernandez-Ojeda et al. 2017). MSG intake has increased to a daily range of 0.3—4 g in industrialised countries. In contrast, a daily intake of up to 1, 4, and 10 g has been reported in Europe, Asia, and Germany, respectively (Sharma et al. 2013; Husarova and Ostatnikova 2013). However, this amount may go higher depending on the content of MSG in the food items and the individual's taste.

Glutamate, a significant component of MSG, is the primary excitatory amino acid neurotransmitter. Excessive glutamate is neurotoxic as it increases neurons' excitability, activates proteolytic enzymes and causes neurotoxicological damage in the hypothalamic neurons and memory impairment in mature mice. Moreover, high concentrations of MSG induced excitotoxicity and cell death in the prefrontal cortex (González-Burgos et al. 2001; Akataobi 2020). This effect can lead to impairment of brain function, neuronal death, and oxidative damage (Srivastava et al. 2014; Ugur Calis et al. 2016). Furthermore, glutamate has been shown to induce oxidative stress via its pro-oxidant activity and stimulates mitochondrial free radical generation due to the overactivation of glutamate receptors (Shah et al. 2015). One of the suggested possible mechanisms by which oxidative damage and lipid peroxidation may be triggered is associated with the involvement of NMDA, GABAA, adrenergic, and D2 receptors, as well as activation of AMPA/kainite receptors (Motaghinejad et al. 2017d, b, c). In addition, degenerative changes were also observed in the neurons and astrocytes due to the neurotoxic effect of MSG, which has been reported in the cerebellum, resulting in cognitive impairment in albino rats (Hashem et al. 2012; Abd El-Hack et al. 2018). Gürgen et al. (2021) reported that MSG caused a decrease in BDNF, NMDA-R, and NPY neural signalling molecules in the CA1 and DG regions of the hippocampus of prepubertal rats compared to the control group. It may be unconnected to the signalling pathway initiated by BDNF (and other receptors) as this plays an essential role in learning and memory formation (Motaghinejad et al. 2017a; Azman and Zakaria 2022).

An abundance of evidence suggests that ATPases such as Ca2+-ATPase, Mg2+-ATPase and Na+/K+-ATPase play an essential role in the maintenance of ionic gradient and nerve cell functions, including the release of signal transduction, neurotransmitters, synaptic plasticity and learning and memory functions in the central nervous system (CNS) (Zaidi 2010; Komali et al. 2021). The neurons of the CNS have the highest activities of these ATPases, possibly due to their high energy demand and their need to maintain normal neuronal function due to fluctuating electrochemical gradients (Nanitsos et al. 2004). It has been shown that a progressive increase in free radical generation and decrease in antioxidant status is an essential contributor to the alteration of ATPases function, which is associated with conformational instability, structural modification and accumulation of inactive or less active forms of enzyme molecules (Stadtman and Berlett 1997; Berlett and Stadtman 1997).

The corpus striatum, also called the striatum, is an essential nucleus in the forebrain and the largest structure in the basal ganglia. It is a group of forebrain structures that include the caudate nucleus, putamen, nucleus accumbens, olfactory tubercule, and globus pallidus. The striatum is part of the brain that controls cognition, reward, coordinated movements, and other vital functions (Yager et al. 2015). Also, the cerebellum is essential in maintaining motor coordination, sensory perception, and control of voluntary movement. The cerebrum is involved in cerebellar learning and is highly susceptible to injury. Thus, damage to this brain region impairs learning, which results in motor disturbances called ataxia (Standring et al. 2005; Reeber et al. 2013).

Vitamin C (ascorbic acid) is a potent non-enzymatic antioxidant with reactive oxygen species (ROS) scavenging properties, forming a relatively stable ascorbate free radical. The ROS scavenging efficiency is due to its electron donor property and its recycling mechanism, which is propagated via NADH- and NADPH-dependent reductases within the cells (Hashem et al. 2012; Rai et al. 2013; Soliman et al. 2018). Neurons maintain high intracellular ascorbic acid concentrations and preserve their redox mechanism balance (Qiu et al. 2007). It has been suggested that the protective capacity of ascorbic acid in the neurons might be related to its involvement in the presynaptic glutamate reuptake, thereby preventing glutamate binding to the NMDA receptor (Liu et al. 2019). Ascorbic acid prevents lipid peroxidation by scavenging the free radicals in the lipid membranes, which has been implicated in preventing degenerative diseases such as cataracts, certain cancers, and cardiovascular diseases (EL-Meghawry EL-Kenawy et al. 2013).

To date, there are contentions on MSG-induced neurological conditions. It has been reported that the blood–brain barrier can effectively restrict the passage of glutamate from the blood into the brain (Fernstrom 2018), except when the amount of MSG is given vastly above normal intake levels. For example, a report showed that among Germans, MSG daily intake via dietary means could be as high as 10 g (Husarova and Ostatnikova 2013). Therefore, this study assessed the modulatory effect of vitamin C treatment on the membrane-bound enzymes such as Ca2+-ATPase, Mg2+-ATPase and Na+/K+-ATPase in high MSG-induced oxidative stress in the striatum and cerebellum of male Wistar rats.

Materials and Methods

Chemicals

MSG was purchased at a store market in Osogbo, Osun State, Nigeria. All the reagents used for the experiment were analytical-grade chemicals procured from Sigma-Aldrich in the USA, Laborchemikalien in Germany, and Merck, Darmstadt in Germany.

Animals and Diets

The male Wistar rats weighing 100—240 g body weights used for this study were purchased from Animal House, Apata, in Ibadan, Oyo State, Nigeria. After being brought to Redeemer's University Animal House, the rats were kept in a standard stainless-steel cage with a wire mesh basement and allowed to acclimatise for eleven (11) days. During the period, rats were given standard rat chow and water. After acclimatisation, rats were randomly grouped.

Experimental Procedures

Rats were grouped randomly into four (4) groups (A – D), with five (5) rats in each group, as presented below:

Monosodium glutamate (15%) is mixed with rat chow in the MSG diet, as previously reported by Adebayo et al. (2011). The feed preparation, including pelletising, was done at Ace Feeds Ltd., Osogbo, Osun State, Nigeria. Rats in each group were fed on a commercial pelleted diet mixed with MSG and drinking water ad libitum for two weeks, after which rats in groups C and D were treated with vitamin C (200 mg−1 kg b.wgt), as previously reported by Adebayo et al. (2019) for additional three weeks. Rats in each group continued on their respective diets until the fifth week. The rats were subjected to a natural photoperiod of 12 h light/12 h dark cycle under standard laboratory conditions, including a well-aerated room with a suitable temperature of 25 ± 2 °C and relative humidity of 55 ± 10%. The procedures on animal handling were approved by the Animal Ethical Committee of Redeemer's University, Osun State, Nigeria (with ethical number RUN/REC/2023/114). They followed the principle of NIH Guidelines for Humane Use and Care of Laboratory Animals. At the end of the 5th week, rats were sacrificed by decapitation after mild anaesthesia using diethyl ether, and brains were quickly removed from the skulls, rinsed in ice-cold normal saline, weighed, and separated into the striatum and cerebellum. The brain regions were stored at -20 °C until required for analyses.

Sample Preparations

The striatum and cerebellum were homogenised in 10% (w/v) of 100 mM phosphate buffer saline (PBS), pH 7.4. The homogenised tissues were spun in a cold centrifuge (4 °C) for 15 min at 4000 rpm. The supernatants were stored at—20 °C and used to determine protein, lipid peroxidation, glutathione levels, and antioxidant activities. Another set of tissues was homogenised in a solution of 0.32 M sucrose buffer, 10 mM Tris–HCl, and 0.5 mM EDTA, pH 7.4. The homogenates were spun in a centrifuge (4 °C) for 15 min at 4000 rpm, and the supernatants obtained were used to determine the activities of membrane-bound enzymes.

Biochemical Assays

Lipid Peroxidation (LPO)

The malondialdehyde (MDA), a marker of lipid peroxidation in the striatum and cerebellum, was measured as described by Ohkawa et al. (1979). Tissue homogenates (250 µL) and an equal volume of tris buffer were incubated at 37 °C for 2 h. To this was added 500 µL of 10% ice-cold TCA, vortexed, and centrifuged at 2,000 g for 10 min. An equal mixture of 500 µL supernatants and 0.67% thiobarbituric acid (TBA) was kept in a boiling water bath for 10 min for colour development. A pink malondialdehyde formed after reacting with thiobarbituric acid was diluted with distilled water and quantified in a spectrophotometer at 532 nm. A molar extinction coefficient of 1.56 × 105 M−1 cm−1 was used for the calculation, and the results were presented as nanomoles MDA per mg protein.

Antioxidant Assays

Catalase (CAT) Activity

CAT activity was estimated using Luck (1971) method. To 3 mL of hydrogen peroxide-phosphate buffer (12.5 mM H2O2 in 0.067 M sodium phosphate buffer, pH 7.0) was added 50 µL of tissues post-nuclear supernatant. The decomposition of hydrogen peroxide by catalase was monitored following a reduction in the absorbance at 240 nm. A molar extinction coefficient of 71 M−1 cm−1 was used for calculation, and the result was expressed as micromoles of H2O2 decomposed/minute/mg protein.

Estimation of Superoxide Dismutase (SOD) Activity

SOD activity was estimated as described by Misra and Fridovich (1972). The principle is based on the inhibition of autoxidation of epinephrine (pH 10.2) at 30 °C. The reaction medium (mixture of 20 µL of sample and 2.5 mL of 0.05 M carbonate buffer (pH 10.2)) was allowed to equilibrate in the cuvette, and 300 µL of 0.3 mM freshly prepared epinephrine solution was added and mixed. The absorbance increase was monitored at 480 nm at an interval of 30 s for 150 s. The activity of SOD was presented as Units/mg of protein.

Determination of Glutathione Level (GSH)

The level of glutathione (GSH) was determined using the method of Roberts and Francetic (1993). A 250 µL tissue supernatant was added to an equal 4% sulfosalicylic acid volume. The mixture was centrifuged at 1200 xg for 5 min. From the supernatant, 250 µL was added to a reaction mixture comprising 2.25 mL of 0.1 mM DTNB prepared in sodium phosphate buffer. The absorbance was measured at 412 nm, and the result was expressed as nanomoles of GSH/mg protein.

Determination of Na+/K+- ATPase Activity

The activity of Na+/K+-ATPase in the striatum and cerebellum homogenates was according to the method of Quigley and Gotterer (1969). The total ATPase was estimated in a reaction medium containing 400 µL of buffered salt solution (7.5 mM MgSO4, 120 mM NaCl, 20 mM KCl) prepared in 75 mM Tris buffer (pH 7.2) and 100 µL of tissue sample. In comparison, the ouabain-sensitive ATPase contained 100 µL of 10 mM ouabain in addition to the reaction mixture for total ATPase. The reaction was initiated by adding 100 µL of 7 mM ATP. The control assay was a mixture of 400 µL and ATP. The three sets of reactions were incubated at 37 °C for 15 min. The reaction was stopped by adding 1 mL of 10% TCA to each tube. Lastly, a 100 µL sample was added to the control tube. The content in each of the three tubes was centrifuged at 3,000 rpm for 10 min, and the inorganic phosphate released was estimated at an absorbance wavelength of 660 nm, as described by Stewart (1974). Disodium hydrogen was used as a standard. The result was presented as nanomoles Pi/minutes/mg protein.

Determination of Ca2+ + Mg2+- ATPase Activity

The activity of Ca2+ + Mg2+-ATPase was estimated as described by Sandhir and Gill (1994). Total ATPase was determined by adding 100 µL sample homogenate to a 400 µL reaction medium containing 37.5 mM MgCl2 and 3.75 mM CaCl2 prepared in 0.3 M Tris–HCl buffer (pH 7.5). Another test tube containing the buffer and the sample was prepared, in addition to 100 µL of 5 mM EGTA. The reaction in both tubes was initiated by adding 100 µL of 8 mM ATP and incubating for 15 min at 37 °C. One millilitre of 50% TCA was added to stop the reaction, and the mixture was centrifuged for 10 min at 3,000 rpm. According to the method of Stewart (1974), the inorganic phosphate released was estimated using disodium hydrogen as the standard. The activity of Ca2+-ATPase was calculated by subtracting the activity of Mg2+-ATPase from the total ATPase. The result was presented as nanomoles Pi/minutes/mg protein.

Statistical Analysis

All data are presented as the mean ± standard deviation and analysed using one-way variance analysis (ANOVA). The significant difference between the evaluations of the rats subjected to monosodium glutamate compared to the control rats fed with rat chow only and those treated with vitamin C were evaluated. Post hoc multiple comparisons were conducted using the Duncan multiple range test to determine the significant differences between the means across groups. The values with p < 0.05 were considered statistically significant. IBM SPSS (Statistical Package for the Social Sciences) software version 23 (Armonk, NY) was used for the analysis.

Results

Effect of MSG and Vitamin C on the Growth Curve, Body, and Brain Weights

As shown in Fig. 1A and Table 1, MSG consumption and vitamin C treatment did not significantly affect the growth curve and body weights compared to the control group. However, in Fig. 1B, MSG consumption significantly increased the striatum weights compared to the control. Control + vitC-treated (CV-treated) (group C) increased striatum weight, but MSG-vitC-treated (MV-treated) (group D) was significantly reduced in the striatum. In contrast, CV-treated and MV-treated with vitamin C did not affect the cerebellum weight.

Fig. 1
figure 1

The growth curve of body weights and the weights of brain regions of MSG and vitamin C-treated rats. 15% MSG was given to the rats along with their normal diet throughout the expirement for 5 weeks and vitamin C was given at a concentration of 200 mg-1 kg b wgt for 3 weeks (A). The weights of the striatum and cerebellum (B). n = 5, and the level of significance was assessed at p < 0.05

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Table 1 Effects of MSG and vitamin C treatments on body weights
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Effect of MSG and Vitamin C on Lipid Peroxidation (LPO) Level

Figure 2A revealed that MSG significantly (p < 0.05) increased the level of LPO in both the striatum and cerebellum. The effect of vitC on the CV-treated (group C) for both brain regions was not statistically (p > 0.05) different from the control group. In contrast, there was a significant reduction (p < 0.05) in the level of LPO of the MV-treated (group D) in both the striatum and cerebellum.

Fig. 2
figure 2

Effect of MSG and vitamin C on lipid peroxidation and antioxidants enzymes. Assessment of the level of MDA, a by-product of lipid peroxidation (A), the acivity of catalase (CAT) (B), the activity of superoxide dismutase (SOD) (C) and assessment of the levels of reduced glutathione (GSH) (D) on MSG- and vitamin C-treated rats. n = 5 *MSG significantly different from the control rats; ‡Control- and MSG-treated significantly different from the untreated group (p < 0.05)

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Effect of MSG and Vitamin C on Catalase (CAT) and Superoxide Dismutase (SOD) Activities

As presented in Fig. 2B & C, the activity of CAT in MSG (group B) was reduced significantly (p < 0.05) in both the striatum and cerebellum when compared to the control (group A). CV-treated with vitamin C was not significant whereas a significant increase was observed in the MV-treated group in the striatum. CV-treated and MV-treated rats significantly (p < 0.05) increased the activity of CAT in the cerebellum. Moreover, MSG significantly (p < 0.05) reduced the activity of SOD in both the striatum and cerebellum. Also, CV-treated and MV-treated groups significantly (p < 0.05) increased the activity of SOD in the striatum and cerebellum.

Effect of MSG and Vitamin C on Glutathione Level

As shown in Fig. 2D, the GSH level reduced significantly (p < 0.05) in both the striatum and cerebellum of the MSG group compared to the control (group A). Moreover, CV-treated and MV-treated groups significantly (p < 0.05) increased the level of GSH in the striatum. Vitamin C treatment did not affect the CV- treated but significantly increased the MV-treated group in the cerebellum.

Effect of MSG and Vitamin C on Na+/K+-ATPase, Ca2+ + Mg2+-ATPase, Mg2+-ATPase and Ca2+-ATPase Activities

As shown in Table 2, compared to the control group (group A), MSG significantly (p < 0.05) decreased Na+/K+-ATPase activity in the striatum and cerebellum. Treatment with vitamin C significantly (p < 0.05) increased Na+/K+-ATPase activity in both the CV-treated and MV-treated striatum and cerebellum. Also, MSG reduced the activities of Ca2+ + Mg2+-ATPase (total ATPase), Mg2+-ATPase, and Ca2+-ATPase in the striatum and cerebellum compared to the control rats. Vitamin C treatment in the CV-treated group did not affect the activities of total ATPase and Ca2+-ATPase in the striatum. Still, both enzyme activities were significantly increased in the MV-treated group. In the cerebellum, the activities of total ATPase, Mg2+-ATPase, and Ca2+-ATPase increased in both the CV-treated and MV-treated groups.

Table 2 Effect of MSG and vitamin C on the activities of Ca2+/ Mg2+-ATPase, Mg2+-ATPase, and Ca2+-ATPase in the striatum and cerebellum of male rats
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Discussion

Monosodium glutamate is widely used as a flavour enhancer that performs physiologic and neuronal functions, including excitatory neurotransmitters. The findings show that MSG and vitamin C did not affect body weight. There are conflicting reports on the effect of MSG on body weight. Some reports indicate that MSG increases body weight compared to the control group (Abdel Moneim et al. 2018), while others show that MSG treatment lowers body weight gain of neonates during lactation (Park and Choi 2016). However, several other reports indicate that MSG ingestion did not affect body weight gain patterns in either mice or rats (Ren et al. 2011; Ashraf et al. 2016; Sreejesh and Sreekumaran 2018; Holton et al. 2019). The results from this study supported the findings of Ashraf et al. (2016) and Holton et al. (2019). The discrepancies might be associated with the administration duration, the MSG dosage, age, and animal species. For example, previous studies have shown that administration of MSG during the neonatal period can cause severe injury to the hypothalamic nuclei region, resulting in increased body weight in rats and accumulation and deposition of fat (Peláez et al. 1999; Nakagawa et al. 2000). This study also shows that MSG increased the weight of the striatum. Glutamate has been reported to act as a positive regulator of neurogenesis and can influence proliferation and neuronal commitment (Schlett 2006). This study observed that MSG speeds up neuron growth and enhances brain cell proliferation (Adebayo et al. 2011). However, MSG ingestion does not affect the cerebellum's weight. This result contradicts the observation of Ashraf et al. (2016), which shows that MSG increases the cerebellum's weight. This was associated with an increased number of Purkinje cells in the brain region after MSG administration (Ashraf et al. 2016). While vitamin C increased the striatal weight of the CV-treated group, a reduction was observed for the MV-treated group, but no effect was observed for cerebellar CV- and MV-treated groups. The reason for this is presently not apparent.

Oxidative stress is an imbalance between oxidants' production and antioxidant defence mechanisms. It is believed to be behind most symptoms and health disorders, causing cellular damage and the progression of several pathological disease conditions (Hassan et al. 2017; Ademiluyi et al. 2020). The brain is susceptible to free radical attack due to the high lipid content, high metabolic rate, and abundant transition metals (Adebayo et al. 2014). The present study shows that MSG significantly increased MDA levels in both the striatum and cerebellum, indicating that MSG results in the excessive generation of free radicals. MSG uses glutamate receptors such as NMDA, AMPA, and kainite receptors as a mechanism of excitotoxicity in neurons (Hernandez-Ojeda et al. 2017). It has been shown that extracellular glutamate with a concomitant influx of calcium activates NMDA, AMPA, and kainate receptors, promoting ROS production in the brain (Zylinska et al. 2023). Furthermore, a report established that activation of NMDA and AMPA/kainate receptors in methylphenidate-induced neurotoxicity in rats triggered oxidative damage and lipid peroxidation (Motaghinejad et al. 2017b). Hussein et al. (2017) stated that MSG-induced-brain oxidative stress is associated with elevated MDA, DNA oxidation, and nitric oxide levels.

Vitamin C treatment decreased MDA levels in both the striatum and cerebellum. Vitamin C concentration in the brain regions is high and thus can modulate glutamatergic neurotransmission because the distribution of glutamatergic NMDA receptors is high in these brain areas (Travica et al. 2017). Moreover, the protective capacity of ascorbic acid in the neurons might be related to its involvement in the presynaptic glutamate reuptake, thereby preventing glutamate binding to the NMDA receptor (Liu et al. 2019). Vitamin C can scavenge free radicals such as superoxide, hydrogen peroxide, and hydroxyl radicals produced in the brain (Airaodion 2019), and this may be connected to its strong reducing and electron donor capacity (Hashem et al. 2012; Adebayo et al. 2019). Furthermore, vitamin C promotes the ability of other antioxidants, such as vitamin E, to break the lipid peroxidation chain in the cell's lipid bilayer (May 2012). The therapeutic efficacy of vitamin C in reducing glutamate-induced phosphorylation of AMP-activated protein kinase (AMPK), resulting in energy depletion and apoptosis in the hippocampus of the developing rat brain, has been reported (Shah et al. 2015).

Striatal and cerebellar exposure to MSG markedly reduced SOD and CAT activities. Reduction of CAT activity in brain tissues following MSG treatment for seven days has been reported (Shivasharan et al. 2013). Also, a decrease in SOD activity was reported in MSG-induced brain injury similar to attention-deficit/hyperactivity disorder (ADHD) (Salem et al. 2022). The reduction in the activities of CAT and SOD may be related to increasing lipid peroxidation, as observed in this study. Moreover, the GSH level decreased in both the striatum and cerebellum. Oxidative stress reduces tissue GSH levels and cellular redox status, and the observation from this study agrees with the reports of Salem et al. (2022) and Hussein et al. (2017). They reported an inverse relationship between glutathione level and lipid peroxidation, thereby causing oxidative stress in the tissues. The depletion of glutathione indicates tissue degeneration, showing that MSG can impair cell defence, leading to cellular injury and impaired neuronal functions. Vitamin C treatment improved the activities of CAT, SOD and GSH in both brain regions. The antioxidant protection of vitamin C may be related to its capacity to donate electrons to hydroxyl, hydrogen peroxide, and superoxide radicals and thus quench their reactivity. Vitamin C is a water-soluble substance with a hydrophilic nature; it protects the antioxidant enzymes of these brain regions by penetrating the blood–brain barrier to scavenge the free radicals (Zhang et al. 2021).

Na+/K+-ATPase regulates ROS and intracellular calcium, and its concentration in the brain signifies its importance in normal brain function. The brain relies on Na+/K+-ATPase to reverse postsynaptic Na+ flux and reestablish Na+-K+ gradients that stimulate astrocytes' neurotransmitter (glutamate) absorption (Adebayo et al. 2015; Al Kahtani 2020). MSG treatment significantly reduced striatal and cerebellar Na+/K+-ATPase, total ATPase, and Ca2+-ATPase activities (Table 2). The reductions might be connected to the enzyme failure arising from free radicals' peroxidation of membrane lipids. Decreases in the activities of Na+/K+-ATPase and Ca2+-ATPase have been reported in protein-undernutrition-induced alterations in Ca2+ homeostasis (Adebayo et al. 2015). Amaral et al. (2012) stated that such reduction might be associated with high vulnerability of brain tissue to free radical attack, contributing to the reduced membrane fluidity of the enzymes.

Furthermore, it has been documented that the continuous presence of MSG in the synapses could lead to overstimulation of glutamate receptors and depolarisation of the postsynaptic membrane. The overstimulation and depolarisation occurred through oxidative glutamate toxicity, which subsequently causes neuronal dysfunction with consequent cell death. The toxicity arises through increased calcium influx coming from free radicals production. Arundine and Tymianski (2004) reported that increased glutamate levels increase calcium overload, resulting in the opening of sodium channels. The influx of Na+ (and Ca2+) ions and efflux of K+ ions causes membrane depolarisation, voltage-dependent calcium channels opening, and removal of magnesium block on the N-methy-D-aspartate (NMDA) receptor, resulting in a higher influx of calcium into the cytosol (Niswender and Conn 2010; Walker and Tesco 2013). The observation from this study shows that vitamin C restored striatal and cerebellar ATPase activities in the MV-treated group. The antioxidant efficacy of vitamin C might be exerted via its antioxidative properties, which allow for the availability of ascorbate (its reduced form) and re-oxidation of dehydroascorbate (oxidised form). Vitamin C protects and restores these pumps' structural and functional integrity and antagonises the toxic effects induced by MSG. It also inhibits redox imbalance produced by stimulating glutamate receptors and the subsequent increase in intracellular calcium (Zylinska et al. 2023).

Conclusion

This work revealed that consumption of high MSG via dietary means for 5 weeks increased lipid peroxidation but reduced antioxidant enzymes and glutathione level in the striatum and cerebellum of male Wistar rats. Also, its consumption results in impaired activities of membrane-bound ATPases (Na+/K+-ATPase, total ATPase, and Ca2+-ATPase). Oral administration of vitamin C (200 mg/Kg body weight) for 3 weeks reversed the toxic effects of MSG on the analysed parameters in these brain regions, supporting its beneficial effects against MSG-induced neurotoxicity. The data in this study clearly portray the protective effect of vitamin C on ATPase activities in MSG-induced striatal and cerebellar oxidative stress. However, the possible mechanism(s) by which vitamin C stabilises ATPase function in both animals and clinical subjects in MSG toxicity await further studies.