• The Korean Journal of Physiology and Pharmacology
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• v.28 no.5
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• pp.413-422
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• 2024

Group I metabotropic glutamate receptors (mGluRs) modulate postsynaptic neuronal excitability and epileptogenesis. We investigated roles of group I mGluRs on low extracellular Mg²⁺ concentration ([Mg²⁺]_o)-induced epileptiform activity and neuronal cell death in the CA1 regions of isolated rat hippocampal slices without the entorhinal cortex using extracellular recording and propidium iodide staining. Exposure to Mg²⁺-free artificial cerebrospinal fluid can induce interictal epileptiform activity in the CA1 regions of rat hippocampal slices. MPEP, a mGluR 5 antagonist, significantly inhibited the spike firing of the low [Mg²⁺]_o-induced epileptiform activity, whereas LY367385, a mGluR1 antagonist, did not. DHPG, a group 1 mGluR agonist, significantly increased the spike firing of the epileptiform activity. U73122, a PLC inhibitor, inhibited the spike firing. Thapsigargin, an ER Ca²⁺-ATPase antagonist, significantly inhibited the spike firing and amplitude of the epileptiform activity. Both the IP₃ receptor antagonist 2-APB and the ryanodine receptor antagonist dantrolene significantly inhibited the spike firing. The PKC inhibitors such as chelerythrine and GF109203X, significantly increased the spike firing. Flufenamic acid, a relatively specific TRPC 1, 4, 5 channel antagonist, significantly inhibited the spike firing, whereas SKF96365, a relatively non-specific TRPC channel antagonist, did not. MPEP significantly decreased low [Mg²⁺]_o DMEM-induced neuronal cell death in the CA1 regions, but LY367385 did not. We suggest that mGluR 5 is involved in low [Mg²⁺]_o-induced interictal epileptiform activity in the CA1 regions of rat hippocampal slices through PLC, release of Ca²⁺ from intracellular stores and PKC and TRPC channels, which could be involved in neuronal cell death.

• Journal of Veterinary Clinics
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• v.27 no.3
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• pp.262-267
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• 2010

Magnesium ($Mg^{2+}$) is an essential co-factor for over 325 physiological and biochemical processes so that plays a central role of neuronal activity, cardiac excitability, neuromuscular transmission, muscular contraction, vasomotor tone, and blood pressure significantly related to physical performance. However, only limited information on blood ionized $Mg^{2+}$ ($iMg^{2+}$) regarding to physical exercise is available and the data from blood total $Mg^{2+}$ detection are inconsistent. This present study investigated the changes of blood $iMg^{2+}$ correlated with metabolic demands during acute high-intensive exhaustive physical exercise in rats. After exhausted swimming (3-4 hours), blood pH, glucose, $HCO_3{^-}$, oxygen and ionized $Ca^{2+}$ ($iCa^{2+}$) were significantly decreased, whereas lactate, carbon dioxide, $iMg^{2+}$, ionized $Na^+$ and ionized $K^+$ were significantly increased. During the exhausted swimming, the changes in $iMg^{2+}$ showed a significant negative correlation with changes in pH, glucose, $HCO_3^-$ and $iCa^{2+}$, however a significant negative correlation with changes in lactate and anionic gap. It is concluded that the acute high-intensive exhaustive physical exercise could produced hypermagnesemia, an increase in blood $iMg^{2+}$ via stimulation of $iMg^{2+}$ efflux following increase in intracellular $iMg^{2+}$ from muscle induced by metabolic and respiratory acidosis.

• Microbiology and Biotechnology Letters
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• v.17 no.4
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• pp.343-348
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• 1989

Production of shikonin derivatives by Lithospermum erythrorhizon cells by using polyurethane foam was invesliigated. Shikonin derivatives were effectively adsorbed mostly by phase distribution to polyurethane matrices and their production increased significantly compared to the suspension culture. The enhanced production of shikonin was probably due to more facilitated cell to cell con-tact and lowered intracellular shikonin concentration, both of which are known to be favorable for plant secondary metabolite production. In order to improve the process productivity, tell culture was conducted under various culture conditions: Of them, Schenk and Hildebrandt medium containing indole-3-acetic acid (1.75mg/ι) and kinetin (0.1mg/ι) was considered most appropriate for shikonin production. Production of shikonin increased about 4.5 times in the Schenk and Hildebrandt medium containing indole-3-acetic acid (1.15mg/ι) and kinetin (0.1mg/ι) when compared to the same medium containing p-chlorophenoxyacetic acid (2.0mg/ι) and kinetin (0.1mg/ι). When poly-urethane was used as the support material, a single-stage system was more preferred to the conventional two-stage culture system in terms of shikonin productivity.

• Archives of Plastic Surgery
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• v.50 no.4
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• pp.432-442
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• 2023

Background Macrophages play a major role in wound healing and prevent infection from the outside. Polarization conversion of macrophages regulates aspects of inflammation, and two macrophages, M1 (classically activated) and M2 (alternatively activated), exist at both ends of broad-spectrum macrophage polarization. Thus, we aimed to investigate whether macrophage polarization can be artificially regulated. To this end, MgSO4 and small-interfering RNA (siRNA) targeting magnesium transport 1 (MAGT1) were used to investigate the effects of intracellular magnesium (Mg2+) concentrations on the differentiation of macrophages in vitro. Methods THP-1 derived macrophages maintained in a culture medium containing 5 mM MgSO4 and siRNA to inhibit the expression of MAGT1. As comparative groups, THP-1 derived macrophages polarized into M1 and M2 macrophages by treatment with M1, M2 inducer cytokine. The polarization status of each group of cells was confirmed by cell surface antigen expression and cytokine secretion. Results We found that MgSO4 treatment increased CD163 and CD206, similar to the effect noted in the M2 group. The expression of CD80 and HLA-DR was increased in the group treated with MAGT1 siRNA, similar to the effect noted in the M1 group. Functional assays demonstrated that the group treated with MgSO4 secreted higher levels of IL-10, whereas the MAGT1 siRNA-treated group secreted higher levels of IL-6 cytokines. Additionally, the conditional medium of the Mg2+ treated group showed enhanced migration of keratinocytes and fibroblasts. Conclusion Mg2+ can help to end the delay in wound healing caused by persistent inflammation in the early stages.

• Food Science and Biotechnology
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• v.17 no.2
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• pp.434-437
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• 2008

The aim of this study was to investigate whether Monascus-fermented soybean extracts (MFSE) containing natural estrogen-like compounds such as isoflavones and mevinolins has potential effects on human osteoblast-like SaOS2 cells using 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) and alkaline phophatase (ALP) assaies. MFSE exerted biphasic dose-dependent effect; stimulating osteoblastic activity at low concentrations and inhibiting SaOS2 cells viability at high concentrations. At $10^{-8}-10^{-4}\;mg/mL$, MFSE is not only non-cytotoxic but also induced comparatively high ALP activity on SaOS2 cells. ALP activity (%) significantly increased (220.1%, p<0.05) when SaOS2 cells were treated with MFSE at a concentration of $10^{-5}\;mg/mL$, whereas slowly increased (185.6%, p<0.05) in unfermented soybean extracts (UFSE) at $10^{-3}\;mg/mL$. The potentially greater ALP activity of MFSE compared to the UFSE might partially be caused by its mevinolin, which was derived from the soybean during Monascus-fermentation. Our findings indicate that supplementation of MFSE may accelerate the speed of intracellular ALP synthesis by the bone cells when provided at optimal dosages.

• Journal of Sasang Constitutional Medicine
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• v.17 no.2
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• pp.64-73
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• 2005

1. Objectives The purpose of this study was to investigate the effects of the enzyme activity of Palmulgunja-tang with administered orally solution on cytochrome P450 isozyme 2. Methods This study was carried on through following methods. We treated the rat with the {3-naphthoflavone (${\beta}NF$) of 80mg/kg for 3 days i.p injection. Firstable, microsomal protein was separated and total intracellular protein test was done. Then GOT and GPT were measured and assay of cytochrome P450 IAI/2 enzyme activity was performed according to the method of EROD and MROD. (Ethoxyresorufin-O-deethylase(EROD) activity was used to measure cytochrome P450 lAI activity and methoxyresorufin O-demethylase(MROD) activity was used to measure cytochrome P450 lA2 activity. ) 3. Results and Conclusions 1) PGT recovered the liver damage on ${\beta}NF$ inducible CYP IAI/2 by pre-post and high-low condition. 2) At concentration of post-treated 50mg!kg of PGT, the inhibiting of $\betaNF$ metabolites to liver of rat cytochrome P450 lAl was inhibited by 53.0% respectively. 3) PGT showed 36.0% inhibition of ${\beta}NF$-induced lA2 activity at the concentration post-treated 50mg/kg.

• Journal of the Korean Society of Food Science and Nutrition
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• v.43 no.10
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• pp.1500-1509
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• 2014

The object of this study was to investigate the inhibitory effects of chios mastic gum (MG) on gastric acid secretion in an ethanol-induced SD rat model and primary parietal cells. Rats were randomly divided into four groups: Vehicle (normal group), Control (treated with ethanol), MG50 (treated with ethanol and mastic gum at 50 mg/kg b.w), MG100 (treated with ethanol and mastic gum at 100 mg/kg b.w). Groups treated with both MG50 and MG100 showed attenuation of gastric mucosal injury, sub-epithelial loss, hemorrhaging, and gastric juice secretion. We also examined the acidity of gastric juice during gastric injury. Oral administration of both MG50 and MG100 significantly decreased acidity of gastric juice by % and %, respectively. To examine the stimulatory factors related to gastric acid secretion, mRNA expression levels of H2r, M3r, CCK2r, and $H^+/K^+$ ATPase were measured by real-time PCR. Compared with a vehicle group, mRNA expression levels of H2r, CCK2r, and $H^+/K^+$ ATPase clearly increased in the control group. However, levels of H2r, CCK2r, and $H^+/K^+$ ATPase slightly but significantly decreased in MG-treated groups compared with control. Blood level of histamine significantly decreased in MG-treated groups, which indicates the involvement of MG on in histamine-related acid secretion. To identify the mode of action of MG in regulating histamine-related pathways, intracellular level of cAMP and mRNA levels of H2r, M3r, CCK2r, and $H^+/K^+$ ATPase were measured in primary parietal cells. While mRNA levels of M3r and CCK2r remained unchanged, levels of H2r and $H^+/K^+$ ATPase significantly decreased upon MG treatment. Subsequently, intracellular levels of cAMP decreased. These results suggest that mastic gum has the ability to inhibit gastric acid secretion by regulating a histamine-related pathway.

• Journal of Korean Biological Nursing Science
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• v.2 no.1
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• pp.49-63
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• 2000

Aflatoxin $B_1(AFB_1)$ is a potent hepatotoxic and hepatocarcinogenic mycotoxin in human beings. It is accumulated in animal tissues and injured cell through variable metabolic pathway. This study was conducted to determine the effect of antioxidant vitamins on liver function enzymes and hepatic damage of $AFB_1$ treated mice. The 6 weeks old male ICR mice were randomly separated 6 groups, vehicle solvent or vitamin C(10 mg/kg/day) and vitamin E(63.8 mg/kg/day) were administered by intraperitoneal(i.p.) injection and 1 hr later, vehicle solution(DMSO) or $AFB_1$(0.4 mg/kg) were injected. The results obtained as follow ; The levels of liver function enzymes such as GOT, GPT, LDH, and alkaline phosphatase, in sera of mice were remarkably elevated by treatment with $AFB_1$ only. However, those enzymes were significantly alleviated by co-treatment with antioxidant vitamins(p<0.01). Especially the levels of LDH and ALK phosphatase were similar to those of control groups(p<0.01). The transmission electron microscopy(TEM) image of intracellular microrganelles on the liver cell of mice was also degenerated extremely by treatment with $AFB_1$, but vitamin C and vitamin E gave good effects on cellular deformation. The intracellular microrganelles such as mitochondria, endoplasmic reticulum, nucleus and nucleic membrane were nearly disappeared the cellular deformation by antioxidant vitamins co-administration. With above results, we could estimated that antioxidant vitamins blocked AFB1 induced hepatic cell damage.

• Korean Journal of Veterinary Research
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• v.36 no.2
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• pp.327-335
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• 1996

Recently in spite of the interest on the regulation of intracellular $Mg^{2+}$ by neurotransmitters or drugs, the magnesium ion($Mg^{2+}$) regulation by ${\alpha}_1$-adrenoceptor stimulation has not been studied in the heart yet. To elucidate the regulation of ${\alpha}_1$-adrenoceptor stimulation-induced $Mg^{2+}$ release and the effects of ${\alpha}_1$-adrenoceptor stimulation on pathophysiological conditions, in this study we have evaluated the effects of phenylephrine, PMA, $H_7$. staurosporine, verapamil and lidocaine on $Mg^{2+}$ release in perfused guinea pig heart. During preperfusion exogenous $Mg^{2+}$ was added to the medium to give 1.2mM 15min before starting to addition of drugs, and then the infusion of exogenous $Mg^{2+}$ was stopped. $Mg^{2+}$ in the perfusate leaving the heart was measured by atomic absorption spectrophotometry. $Mg^{2+}$ free solution produced an increase in heart rate and phenylephrine elicited $Mg^{2+}$ release from the heart. $Mg^{2+}$ release by phenylephrine was abolished by combined treatment with prazosin. By contrast, cardiac $Mg^{2+}$ uptake induced by a protein kinase C(PKC) activator, PMA was abolished by a selective PKC inhibitor, staurosporine. And the phenylephrine-induced $Mg^{2+}$ release was not affected by the PKC inhibitor, $H_7$. When verapamil or lidocaine was added to perfusing solution, $Mg^{2+}$ release was potentiated by phenylephrine from perfused guinea pig heart. These results suggest that ${\alpha}_1$-adrenoceptor stimulation caused $Mg^{2+}$ release and that PKC is not involved in ${\alpha}_1$-adrenoceptor mediated $Mg^{2+}$ release from perfused guinea pig heart. Under pathophysiological conditions, the $Mg^{2+}$ alteration by ${\alpha}_1$-adrenoceptor stimulation is considerable.

• Korean Journal of Veterinary Research
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• v.38 no.1
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• pp.29-42
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• 1998

$Mg^{2+}$ is one of the most abundant divalent cations in mammalian body(0.2~1.0mM) and the important physiological roles are : first, the cofactor of many enzyme activities, second, the regulator of glycolysis and DNA synthesis, third, the important role of bioenergetics by regulating of phosphorylation, fourth, the influence of cardiac metabolism and function. In this work we have investigated the regulation of the $Mg^{2+}$ induced by ${\alpha}_1-adrenoceptor$ stimulation in perfused guinea pig hearts and isolated myocytes. The $Mg^{2+}$ content of the perfusate or the supernatant was measured by atomic absorbance spectrophotometry. The elimination of $Mg^{2+}$ in the medium increased the force of contraction of right ventricular papillary muscles, and the left ventricular pressure. Phenylephrine also enhanced the force of contraction in the presence of $Mg^{2+}-free$ medium. ${\alpha}_1-Agonists$ such as phenylephrine and methoxamine were found to induce $Mg^{2+}$ efflux in both perfused hearts and myocytes. These effects were blocked by prazosin, an ${\alpha}_1-adrenoceptor$ antagonist. The $Mg^{2+}$ influx could also be induced by phenylephrine and R59022, a diacylglycerol kinase inhibitor. In the presence of protein kinase C(PKC) inhibitors, phenylephrine produced an increase in $Mg^{2+}$ efflux from perfused hearts. Furthermore, $Mg^{2+}$ efflux by phenylephrine was amplified by phorbol 12-myristate 13-acetate(PMA). This enhancement of $Mg^{2+}$ efflux by PMA was blocked by prazosin in perfused hearts. By contrast, the $Mg^{2+}$ influx could be induced by verapamil, nifedipine, ryanodine in perfused hearts, but not in myocytes. $W^7$, a $Ca^{2+}$/calmodulin antagonist, completely blocked the phenylephrine-induced $Mg^{2+}$ efflux in perfused hearts. In conclusion, $Mg^{2+}$ is responsible for the cardiac activity associated with ${\alpha}_1-adrenoceptor$ stimulation. The mobilization of $Mg^{2+}$ is decreased or increased by ${\alpha}_1-adrenoceptor$ stimulation in guinea pig hearts. These responses may be related specifically to the respective pathways of signal transduction. A decrease in $Mg^{2+}$ efflux by ${\alpha}_1-adrenoceptor$ stimulation in hearts can be through PKC dependent and intracellular $Ca^{2+}$ levels.