• The Korean Journal of Physiology and Pharmacology
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• v.2 no.2
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• pp.225-232
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• 1998

To investigate the possible involvement of outward potassium ($K^+$) currents in nitric oxide-induced relaxation in intestinal smooth muscle, we used whole-cell patch clamp technique in freshly dispersed guinea-pig ileum longitudinal smooth muscle cells. When cells were held at -60 mV and depolarized from -40 mV to -50 mV in 10 mV increments, sustained outward $K^+$ currents were evoked. The outward $K^+$ currents were markedly increased by the addition of 10 ${\mu}M$ sodium nitroprusside (SNP). 10 ${\mu}M$ S-nitroso-N-acetylpenicillamine (SNAP) and 1 mM 8-Bromo-cyclic GMP (8-Br-cGMP) also showed a similar effect to that of SNP. 1 mM tetraethylammonium (TEA) significantly reduced depolarization-activated outward $K^+$ currents. SNP-enhanced outward $K^+$ currents were blocked by the application of TEA. High EGTA containing pipette solution (10 mM) reduced the control currents and also inhibited the SNP-enhanced outward $K^+$ currents. 5 mM 4-aminopyridine (4-AP) significantly reduced the control currents but showed no effect on SNP-enhanced outward $K^+$ currents. 0.3 ${\mu}M$ apamin and 10 ${\mu}M$ glibenclamide showed no effect on SNP-enhanced outward $K^+$ currents. 10 ${\mu}M$ 1H-[1,2,4]oxadiazolo [4,3-a]quinoxaline-1-one (ODQ), a specific inhibitor of soluble guanylate cyclase, significantly blocked SNP-enhanced $K^+$ currents. We conclude that NO donors activate the $Ca^{2+}-activated$ $K^+$ channels in guinea-pig ileal smooth muscle via activation of guanylate cyclase.

• Toxicological Research
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• v.34 no.4
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• pp.291-296
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• 2018

Chemical carcinogenesis is a multistep process. Genotoxic carcinogens, which are DNA-reactive, induce DNA adduct formation and genetic alterations in target cells, thereby generating mutated cells (initiation). Subsequently, preneoplastic lesions appear through clonal proliferation of the mutated cells and transform into tumors (promotion and progression). Many factors may influence these processes in a dose-dependent manner. Therefore, quantitative analysis plays an important role in studies on the carcinogenic threshold of genotoxic carcinogens. Herein, we present data on the relationship between key carcinogenic events and their deriving point of departure (PoD). Their PoDs were also compared to those of the carcinogenesis pathway. In an experiment, the liver of rats exposed to 2-amino-3,8-dimethylimidazo-(4,5-f)quinoxaline (MeIQx) was examined to determine the formation of MeIQx-DNA adducts, generation of mutations at LacI transgene, and induction of preneoplastic glutathione S-transferase placental form (GST-P)-positive foci and tumors (benign and malignant). The PoDs of the above key events in the carcinogenicity of MeIQx were increased as the carcinogenesis advanced; however, these PoDs were lower than those of tumor induction. Thus, the order of key events during tumor induction in the liver was as follows: formation of DNA adducts ${\ll}$ Mutations ${\ll}$ GST-positive foci (preneoplasia) ${\ll}$ Tumor (adenoma and carcinoma). We also obtained similar data on the genotoxic and carcinogenic PoDs of other hepatocarcinogens, such as 2-amino-3,8-dimethylimidazo(4,5-f)quinoline. These results contribute to elucidating the existence of a genotoxic and carcinogenic threshold.

• Environmental Mutagens and Carcinogens
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• v.18 no.1
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• pp.26-31
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• 1998

Antimutagenic activity of Saururus chinesis (Lour.) Bail was investigated for food-borne mutagens using S. typhimurium TA98. Methanol extract from Saururus Chinesis (Lour.) Bail was fractionated into hexane, chloroform, ethylacetate and butanol fractions, followed by determination of antimutagenic activity for food-borne mutagenic heterogenic amines (HCA). The hexane fraction exhibited a strong antimutagenic activity for 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-3,8-dimethylimidazo[4,5-f] quinoxaline (MeIQ), 2-amino-3,4-dimethyl-3H-imidazo[4,5-f]quinoline (MeIQx), 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 3-amino-1-methyl-5H-pyroid[4,3-b]indole acetate (Trp-2-A); however its fraction rather enhanced the bacterial mutagenicity of 2-amino-3,4,8-trimethyl-3H-imidazo[4,5-f]quinozaline (4,8-diMeIQx) and 2-amino-3,7,8-trimethyl-3H-imidazo[4,5-f]quinoxline (7,8-diMeIQx). Active principle in the fraction was found to be two major compounds (${\gamma}$-crene B and epi-bicyclosesquiphellandrane) and 6 minor compounds (${\delta}$-caryophyllene, ${\gamma}$-elemene, ${\beta}$-cabebene, ${\delta}$-cadinene, ${\delta}$-selinene, and patchoulene). Modulation effect for the mutagenic activity of the food-borne mutagenic HCA by the fraction might be derived from a cumulative effect of each individual compounds. Hence, this hexane fraction might be use to reduce the production of mutagenic HCA during cooking process of protein-rich foods.

• Journal of Oriental Neuropsychiatry
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• v.24 no.3
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• pp.271-280
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• 2013

Objectives : The development of natural drugs with antidepressant effects is important and needed. This study was performed to investigate the antidepressant-like effects of the distilled water extract of Portulaca oleracea L. (POL) in a mouse model and to investigate the role of ${\alpha}$-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptors in producing these antidepressant-like effects. Methods : The forced swim test (FST) and tail suspension test (TST) were used to investigate the behavioral anti-depressive-like effects of POL in mice. Additional behavioral experiments with 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo[f]quinoxaline-2,3-dione, an AMPA receptor antagonist, were undertaken to determine the involvement of the antidepressant-like properties of POL in AMPA receptor throughput. Results : Oral administration of the POL extract (100 mg/kg) 1 h prior to testing significantly reduced the immobility times in the FST and TST. The antidepressant-like effects of the POL extract were not increased in a dose-dependent manner. Pre-treatment with NBQX significantly attenuated the reduction in immobility time induced by the POL extract in the FST. Conclusions : The distilled water extract of POL has antidepressant-like effects, which may be related to AMPA receptor. Pre-treatment with NBQX significantly attenuates the reduction in immobility time induced by the POL extract in the FST.

• The Korean Journal of Physiology and Pharmacology
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• v.9 no.5
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• pp.255-262
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• 2005

Striatum is involved in the control of movement and habitual memory. It receives glutamatergic input from wide area of the cerebral cortex as well as an extensive serotonergic (5-hydroxytryptamine, 5-HT) input from the raphe nuclei. In our study, the effects of 5-HT on synaptic transmission were studied in the rat corticostriatal brain slice using in vitro whole-cell recording technique. 5-HT inhibited the amplitude as well as frequency of spontaneous excitatory postsynaptic currents (sEPSC) significantly, and neither ${\gamma}-aminobutyric$ acid (GABA)A receptor antagonist bicuculline (BIC), nor $N-methyl-_{D}-aspartate$ (NMDA) receptor antagonist, $_{DL}-2-amino-5-phosphonovaleric$ acid (AP-V) could block the effect of 5-HT. In the presence non-NMDA receptor antagonist, 2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenxo[f] quinoxaline-7-sulfonamide (NBQX), the inhibitory effect of 5-HT was blocked. We also figured out that 5-HT change the channel kinetics of the sEPSC. There was a significant increase in the rise time during the 5-HT application. Our results suggest that 5-HT has an effect on both pre- and postsynaptic site with decreasing neurotransmitter release probability of glutamate and decreasing the sensitivity to glutamate by increasing the rise time of non-NMDA receptor mediated synaptic transmission in the corticostriatal synapses.

• YAKHAK HOEJI
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• v.49 no.4
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• pp.347-354
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• 2005

Lipopolysaccharide (LPS) induces synthesis of several inflammatory cytokines and nitric oxide (NO). NO in brain is involved not only in the regulation of important metabolic pathways via intracellular cyclic GMP-dependent path­ways, but also in neurotoxic damage by reacting with superoxide ion leading to form peroxynitrite radical. Oxidative stress has suggested to be related to the inhibition of NO synthase/cyclic GMP pathway. OQ21 is a new fluorinated quinone compound that is recently known to have inhibitory effects on both NO synthase (NOS) and guanylyl cyclase (GC). In this study, we examined effects of OQ21, other known NOS or GC inhibitors, or an antioxidant, melatonin, on the oxidative stress produced by LPS in rat brain. Oxidative stress was observed by using the 2',7'-dichlorofluorescin diacetate to measure intra-cellular reactive oxygen species (ROS) production and by measuring the formation of thiobarbituric acid reactive substances to measure lipid peroxidation. LPS induced significant increase in both ROS produdction and lipid peroxidation in all brain regions tested (striatum, hippocampus and cortex), which were dissected 6hr after intraperitoneal administration of LPS to rats. Direct striatal injection of two NOS inhibitors, N-nitro-L-arginine methyl ester and diphenyleneiodonium, or a GC inhibitor, IH-[1,2,4]oxadiazolo[4,3-a]quinoxaline-l-one, produced no significant ROS increase. However, OQ21 enhanced ROS formation in striatal tissues from LPS-treated rats. Melatonin decreased LPS-induced ROS formation and decreased ROS formation increased by OQ21 in striatum of LPS-treated rats.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.31 no.6
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• pp.835-841
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• 1998

The antimicrobial activities of horseradish ( Wasahia japonica) root extract against 4 kinds of food poisoning bacteria and 3 kinds of molfs were examined. The antimutagenic activity of horseradish ( Wasahia japonica) root extracts was also examined by Ames test with Salmonella tyhimurium TA 98 The antimicrobial activities of distilled water extracts from horseradish root were stronger than those of ethanol extracts, and stronger against molds than bacteria. Of the kinds of bacteria, Vibrio parahaemolyticus was best inhibited by the distilled water extracts from horseradish root. The antimicrobial activity of distilled water extracts from horseradish root were stronger against 3-Amino-1, 4-dimethyl-5H-pyrido{4,3-b}indole than 2-Amino-3,-8-dimethylimidazo-[4,5-f]quinoxaline.

• Journal of Microbiology
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• v.34 no.2
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• pp.192-197
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• 1996

L-Xylosone was detected as its quinoxaline derivative in the degradation solution of dehydro-L-ascorbic acid. The production rate of L-xylosone was much faster in aerated phosphate-cirate buffer (pH 5. 6) than in pure water. L-Xylosone and dehydro-L-ascorbic acid were identified in the crude extracts of Saccharomyces cerevisiae. The concentration of L-xylosone in the crude cell extracts was calculated to be about 0.2 nmol $(mg protein)^{-1}$. When L-xylosone was added to asynchronous culture of S. cerevisiae, it inhibited primarily the synthesis of protein and RNA. Examination of the effect of L- xylosone on synchronous culture of the yeast indicated that L-xylosone inhibited the initiation of DNA replication and that the cells were arrested at $G_1$, stage of cell division cycle. These results suggested a possibility that L-xylosone can act as an inhibitor of cell growth.

• The Korean Journal of Physiology and Pharmacology
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• v.24 no.5
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• pp.433-440
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• 2020

The substantia gelatinosa (SG) of the trigeminal subnucleus caudalis (Vc) is the first relay site for the orofacial nociceptive inputs via the thin myelinated Aδ and unmyelinated C primary afferent fibers. Borneol, one of the valuable time-honored herbal ingredients in traditional Chinese medicine, is a popular treatment for anxiety, anesthesia, and antinociception. However, to date, little is known as to how borneol acts on the SG neurons of the Vc. To close this gap, the whole-cell patch-clamp technique was applied to elucidate the antinociceptive mechanism responding for the actions of borneol on the SG neurons of the Vc in mice. In the voltage-clamp mode, holding at -60 mV, the borneol-induced non-desensitizing inward currents were not affected by tetrodotoxin, a voltage-gated Na⁺ channel blocker, 6-cyano-7-nitro-quinoxaline-2,3-dione, a non-N-methyl-ᴅ-aspartate (NMDA) glutamate receptor antagonist and DL-2-amino-5-phosphonopentanoic acid, an NMDA receptor antagonist. However, borneol-induced inward currents were partially decreased in the presence of picrotoxin, a γ-aminobutyric acid (GABA)_A receptor antagonist, or strychnine, a glycine receptor antagonist, and was almost suppressed in the presence of picrotoxin and strychnine. Though borneol did not show any effect on the glycine-induced inward currents, borneol enhanced GABA-mediated responses. Beside, borneol enhanced the GABA-induced hyperpolarization under the current-clamp mode. Altogether, we suggest that borneol contributes in part toward mediating the inhibitory GABA and glycine transmission on the SG neurons of the Vc and may serve as an herbal therapeutic for orofacial pain ailments.

• Journal of People, Plants, and Environment
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• v.23 no.4
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• pp.399-410
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• 2020

The United Nations project the world population to reach 10 billion by the year 2057. To increase the food of the ever-increasing world population, agrochemicals are indispensable tools to the boon in agriculture production. These agrochemicals are a serious threat to the health of humans, plants, and animals. Agrochemicals are ultimately reached to the main reservoir/sink such as soil and contaminating the groundwater, disturb the soil health and in turn a serious threat to biogeochemical cycling and the entire biosphere. Among agrochemicals, quinalphosis one of the most repeatedly and widely used insecticides in the control of a wide range of pests that attack various crops. Quinalphos is shown to be primarily toxic in organisms by acetylcholinesterase enzyme action. Hydrolysis of quinalphos produces amajor metabolite 2-hydroxyquinoxaline (2-HQ), which has shown secondary toxicity in organisms. 2-HQ is reported to be mutagenic, carcinogenic, growth inhibition and induce oxidative stress in organisms. Quinoline is a heterocyclic compound and structural resemblance of 2-HQ with minor changes, but its degradation studies are enormous compared to the 2-HQ compound. Biotic factors in fate and behavior of 2-HQ in the environment are least studied. 2-HQ interactions with soil enzymes are vary from soil to soil. Based on the toxicity of 2-HQ in our stockpile we need to isolate a handful of microorganisms to treat this persistent metabolite and also other metabolites/compounds.This brief review will be significant from the point of biological and environmental safety.