Protective autoimmunity against the enemy within: fighting glutamate toxicity

Monosodium glutamate is naturally available non-essential amino acids, which found in naturally occurring foods and used as flavour enhancer worldwide. Monosodium glutamate is believed to be linked with diverse health problems. The aim of the study was toxic effects of monosodium glutamate (MSG) and the protective role of L-carnitine, light on the available literature from last 25 years about diverse toxicity studies which had been carried out on animal and human models. Google scholar, NCBI, PUBMED, EMBASE, Wangfang databases, and Web of Science databases were used to retrieve the available studies. MSG was linked with deleterious effects particularly in animals including induction of obesity, diabetes, hepatotoxic, neurotoxic and genotoxic effects showed in Literature. Few reports revealed increased hunger, food intake, and obesity in human subjects due to MSG consumption. Hepatotoxic, neurotoxic, and genotoxic effects of monosodium glutamate on humans carried out very limitedly. High consumption of monosodium glutamate may be linked with harmful health effects showed in available literatures. So, it is recommended to use common salt instead of MSG. Furthermore, intensive research is required to explore monosodium glutamate–related molecular and metabolic mechanisms. L-carnitine can protect from Hepatotoxic, neurotoxic, renal impairment and genotoxic effects functionally, biochemically and histopathologically with a corresponding reduction of oxidative stress.

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Protective Effect of Osmundacetone against Neurological Cell Death Caused by Oxidative Glutamate Toxicity

Biomolecules ◽

10.3390/biom11020328 ◽

2021 ◽

Vol 11 (2) ◽

pp. 328

Author(s):

Tuy An Trinh ◽

Young Hye Seo ◽

Sungyoul Choi ◽

Jun Lee ◽

Ki Sung Kang

Keyword(s):

Oxidative Stress ◽

Cell Death ◽

Defense Mechanism ◽

Neuroprotective Effect ◽

Glutamate Release ◽

Chromatin Condensation ◽

Critical Role ◽

Glutamate Toxicity ◽

Heme Oxygenase 1 ◽

Brain Functions

Oxidative stress is one of the main causes of brain cell death in neurological disorders. The use of natural antioxidants to maintain redox homeostasis contributes to alleviating neurodegeneration. Glutamate is an excitatory neurotransmitter that plays a critical role in many brain functions. However, excessive glutamate release induces excitotoxicity and oxidative stress, leading to programmed cell death. Our study aimed to evaluate the effect of osmundacetone (OAC), isolated from Elsholtzia ciliata (Thunb.) Hylander, against glutamate-induced oxidative toxicity in HT22 hippocampal cells. The effect of OAC treatment on excess reactive oxygen species (ROS), intracellular calcium levels, chromatin condensation, apoptosis, and the expression level of oxidative stress-related proteins was evaluated. OAC showed a neuroprotective effect against glutamate toxicity at a concentration of 2 μM. By diminishing the accumulation of ROS, as well as stimulating the expression of heat shock protein 70 (HSP70) and heme oxygenase-1 (HO-1), OAC triggered the self-defense mechanism in neuronal cells. The anti-apoptotic effect of OAC was demonstrated through its inhibition of chromatin condensation, calcium accumulation, and reduction of apoptotic cells. OAC significantly suppressed the phosphorylation of mitogen-activated protein kinases (MAPKs), including c-Jun NH2-terminal kinase (JNK), extracellular signal-regulated kinase (ERK), and p38 kinases. Thus, OAC could be a potential agent for supportive treatment of neurodegenerative diseases.

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Quercetin attenuates the reduction of parvalbumin in middle cerebral artery occlusion animal model

Laboratory Animal Research ◽

10.1186/s42826-021-00086-0 ◽

2021 ◽

Vol 37 (1) ◽

Author(s):

Dong-Ju Park ◽

Ju-Bin Kang ◽

Fawad-Ali Shah ◽

Phil-Ok Koh

Keyword(s):

Middle Cerebral Artery ◽

Middle Cerebral Artery Occlusion ◽

Cerebral Artery ◽

Neuroprotective Effect ◽

Neuronal Cell ◽

Artery Occlusion ◽

Male Rats ◽

Neurological Deficits ◽

Glutamate Toxicity ◽

Cerebral Artery Occlusion

Abstract Background Calcium is a critical factor involved in modulation of essential cellular functions. Parvalbumin is a calcium buffering protein that regulates intracellular calcium concentrations. It prevents rises in calcium concentrations and inhibits apoptotic processes during ischemic injury. Quercetin exerts potent antioxidant and anti-apoptotic effects during brain ischemia. We investigated whether quercetin can regulate parvalbumin expression in cerebral ischemia and glutamate toxicity-induced neuronal cell death. Adult male rats were treated with vehicle or quercetin (10 mg/kg) 30 min prior to middle cerebral artery occlusion (MCAO) and cerebral cortical tissues were collected 24 h after MCAO. We used various techniques including Western blot, reverse transcription-PCR, and immunohistochemical staining to elucidate the changes of parvalbumin expression. Results Quercetin ameliorated MCAO-induced neurological deficits and behavioral changes. Moreover, quercetin prevented MCAO-induced a decrease in parvalbumin expression. Conclusions These findings suggest that quercetin exerts a neuroprotective effect through regulation of parvalbumin expression.

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GLT1 gene delivery based on bone marrow-derived cells ameliorates motor function and survival in a mouse model of ALS

Scientific Reports ◽

10.1038/s41598-021-92285-x ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Natsuko Ohashi ◽

Tomoya Terashima ◽

Miwako Katagi ◽

Yuki Nakae ◽

Junko Okano ◽

...

Keyword(s):

Spinal Cord ◽

Gene Therapy ◽

Bone Marrow ◽

Mouse Model ◽

Lentiviral Vector ◽

White Blood Cells ◽

Glutamate Toxicity ◽

Pathological Lesion ◽

Arginase 1 ◽

Therapy Strategy

AbstractAmyotrophic lateral sclerosis (ALS) is an intractable neurodegenerative disease. CD68-positive bone marrow (BM)-derived cells (BMDCs) accumulate in the pathological lesion in the SOD1(G93A) ALS mouse model after BM transplantation (BMT). Therefore, we investigated whether BMDCs can be applied as gene carriers for cell-based gene therapy by employing the accumulation of BMDCs. In ALS mice, YFP reporter signals were observed in 12–14% of white blood cells (WBCs) and in the spinal cord via transplantation of BM after lentiviral vector (LV) infection. After confirmation of gene transduction by LV with the CD68 promoter in 4–7% of WBCs and in the spinal cord of ALS mice, BM cells were infected with LVs expressing glutamate transporter (GLT) 1 that protects neurons from glutamate toxicity, driven by the CD68 promoter, which were transplanted into ALS mice. The treated mice showed improvement of motor behaviors and prolonged survival. Additionally, interleukin (IL)-1β was significantly suppressed, and IL-4, arginase 1, and FIZZ were significantly increased in the mice. These results suggested that GLT1 expression by BMDCs improved the spinal cord environment. Therefore, our gene therapy strategy may be applied to treat neurodegenerative diseases such as ALS in which BMDCs accumulate in the pathological lesion by BMT.

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