• Journal of Pharmacopuncture
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• v.19 no.3
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• pp.213-224
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• 2016

Objectives: Ginseng Rh2+ is enzyme-treated ginseng extract containing high amounts of converted ginsenosides, such as compound k, Rh2, Rg3, which have potent anticancer activity. We conducted general and genetic toxicity tests to evaluate the safety of ginseng Rh2+. Methods: An acute oral toxicity test was performed at a high-level dose of 4,000 mg/kg/day in Sprague-Dawley (SD) rats. A 14-day range-finding study was also conducted to set dose levels for the 90-day study. A subchronic 90-day toxicity study was performed at dose levels of 1,000 and 2,000 mg/kg/day to investigate the no-observed-adverse-effect level (NOAEL) of ginseng Rh2+ and target organs. To identify the mutagenic potential of ginseng Rh2+, we conducted a bacterial reverse mutation test (Ames test) using amino-acid-requiring strains of Salmonella typhimurium and Escherichia coli (E. coli), a chromosome aberration test with Chinese hamster lung (CHL) cells, and an in vivo micronucleus test using ICR mice bone marrow as recommended by the Korean Ministry of Food and Drug Safety. Results: According to the results of the acute oral toxicity study, the approximate lethal dose (ALD) of ginseng Rh2+ was estimated to be higher than 4,000 mg/kg. For the 90-day study, no toxicological effect of ginseng Rh2+ was observed in body-weight changes, food consumption, clinical signs, organ weights, histopathology, ophthalmology, and clinical pathology. The NOAEL of ginseng Rh2+ was established to be 2,000 mg/kg/day, and no target organ was found in this test. In addition, no evidence of mutagenicity was found either on the in vitro genotoxicity tests, including the Ames test and the chromosome aberration test, or on the in vivo in mice bone marrow micronucleus test. Conclusion: On the basis of our findings, ginseng Rh2+ is a non-toxic material with no genotoxicity. We expect that ginseng Rh2+ may be used as a novel adjuvant anticancer agent that is safe for long-term administration.

• The Korean Journal of Physiology and Pharmacology
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• v.23 no.2
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• pp.121-130
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• 2019

Glutamate toxicity-mediated mitochondrial dysfunction and neuronal cell death are involved in the pathogenesis of several neurodegenerative diseases as well as acute brain ischemia/stroke. In this study, we investigated the neuroprotective mechanism of dieckol (DEK), one of the phlorotannins isolated from the marine brown alga Ecklonia cava, against glutamate toxicity. Primary cortical neurons ($100{\mu}M$, 24 h) and HT22 neurons (5 mM, 12 h) were stimulated with glutamate to induce glutamate toxic condition. The results demonstrated that DEK treatment significantly increased cell viability in a dose-dependent manner ($1-50{\mu}M$) and recovered morphological deterioration in glutamate-stimulated neurons. In addition, DEK strongly attenuated intracellular reactive oxygen species (ROS) levels, mitochondrial overload of $Ca^{2+}$ and ROS, mitochondrial membrane potential (${\Delta}{\Psi}_m$) disruption, adenine triphosphate depletion. DEK showed free radical scavenging activity in the cell-free system. Furthermore, DEK enhanced protein expression of heme oxygenase-1 (HO-1), an important anti-oxidant enzyme, via the nuclear translocation of nuclear factor-like 2 (Nrf2). Taken together, we conclude that DEK exerts neuroprotective activities against glutamate toxicity through its direct free radical scavenging property and the Nrf-2/HO-1 pathway activation.

• Journal of Embryo Transfer
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• v.26 no.4
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• pp.257-263
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• 2011

BPA, a diphenyl compound containing groups, that make it structurally similar to synthetic estrogen and is considered as one of the major endocrine disruptors. Silymarin has extensively been used to prevent and/or alleviate some human disease, especially for the treatment of adverse liver conditions. It has an antioxidative efficacy and cancer preventive efficacy. Therefore, we examined the hypothesis that silymarin can inhibit BPA-induced toxicity in boar sperm duing in vitro storage. Sperm characteristics (motility, viability, membrane integrity and mitochondrion activity) in semen exposed to BPA (10~200 uM) were sharply lowered, while it increase in a dose and time dependent manner due to silymarin addition (50~200 uM) into semen extender in the presence of BPA (100 uM). All of the evaluated characteristics were gradually improved in the groups that were treated with silymarin (50~200 uM) in the presence of BPA (100 uM) in comparison to BPA 100 uM alone group, irrespective of incubation periods (3 and 6 h). These results demonstrate that silymarin can ameliorate the toxicity of BPA on boar sperm characteristics during in vitro storage, suggesting that silymarin indirectly act as an antioxidant.

• Korean Journal of Pharmacognosy
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• v.31 no.1
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• pp.7-15
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• 2000

Glycyrrhizae Radix aqua-acupuncture solution (GRAS) and Glycyrrhizae Radix water-extracted solution (GRWS) were prepared and tested for organ toxicities, antitumor activities, and immunomodulatory effects. The organ-toxicity of GRAS to male ICR mice was studied by the measurements of glutamic oxaloacetic transaminase (GOT), glutamic pyruvate transaminase (GPT), lactate dehydrogenase (LDH), and alkaline phosphatase (ALP-s) activities after injection of GRAS for 7 days. The activities of GOT, GPT, LDH, ALP-s were decreased with GRAS. It was shown to possess considerable toxicity toward various tumor cell lines. Concentration of GRAS at 1.5g/ml and 3g/ml resulted in more than 80% inhibition of growth in Ehrlich ascites tumor cells (EATC), Hepa1c1c7, and HeLa cells. Toxicity of GRAS to A549 revealed that 68% inhibition of growth. GRWS at the concentration of 3g/ml showed more than 80% inhibition of growth with EATC, Hepalclc7, A549 and HeLa. In morphological study, the number of cells were decreased, and the shape of cells was round-form in EATC, Hepalclc7, A549 and HeLa cells with GRAS. Administration of GRAS inhibited the growth of EATC in vivo. Mice given EATC at 1.5g/ml or 0.3g/ml GRAS had 16.7% to 50% survival after 21 days. GRAS increased the proliferation of T and B cells and the cytolytic activity of purified T cell. The biosyntheses of nucleic acid and protein of EATC, Hepalclc7, A549 and HeLa cells were inhibited by GRAS.

• Toxicological Research
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• v.31 no.3
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• pp.313-319
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• 2015

3-Monochloro-1,2-propanediol (3-MCPD) and 1,3-dichloro-2-propanol (1,3-DCP) are not only produced in the manufacturing process of foodstuffs such as hydrolyzed vegetable proteins and soy sauce but are also formed by heat processing in the presence of fat and low water activity. 3-MCPD exists both in free and ester forms, and the ester form has been also detected in various foods. Free 3-MCPD and 1,3-DCP are classified as Group 2B by the International Agency for Research on Cancer. Although there is no data confirming the toxicity of either compound in humans, their toxicity was evidenced in animal experimentation or in vitro. Although few studies have been conducted, free 3-MCPD has been shown to have neurotoxicity, reproductive toxicity, and carcinogenicity. In contrast, 1,3-DCP only has mutagenic activity. The purpose of this study was to analyze 3-MCPD and 1,3-DCP in various foods using gas chromatography-mass spectrometry. 3-MCPD and 1,3-DCP were analyzed using phenyl boronic acid derivatization and the liquid-liquid extraction method, respectively. The analytical method for 3-MCPD and 1,3-DCP was validated in terms of linearity, limit of detection (LOD), limit of quantitation, accuracy and precision. Consequently, the LODs of 3-MCPD and 1,3-DCP in various matrices were identified to be in the ranges of 4.18~10.56 ng/g and 1.06~3.15 ng/g, respectively.

• Journal of Korean Society of Environmental Engineers
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• v.31 no.12
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• pp.1069-1074
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• 2009

This study investigated soil microbial community and growth of Zea mays to compare the toxicity of nano and micro-sized Cu and Zn oxide particles in microcosm system. In the presence of nanoparticles, biomass of Zea mays reduced by 30% compared with micro-sized particles and inhibited growth. Dehydrogenase activity was inhibited by CuO nano although it was increased by ZnO nano particles. According to the Biolog test, the microbial diversity was decreased after exposed to CuO nanoparticles and ZnO microparticles. Therefore, though it is widely recognized that nanoparticles are more harmful than microparticles, we can conclude that the diversity of microbial community does not always influenced by the size of particles of nano and micro.

• Journal of Microbiology and Biotechnology
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• v.23 no.8
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• pp.1107-1115
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• 2013

The Cyt1Aa protein of Bacillus thuringiensis susbp. israelensis elaborates demonstrable toxicity to mosquito larvae, but more importantly, it enhances the larvicidal activity of this species Cry proteins (Cry11Aa, Cry4Aa, and Cry4Ba) and delays the phenotypic expression of resistance to these that has evolved in Culex quinquefasciatus. It is also known that Cyt1Aa, which is highly lipophilic, synergizes Cry11Aa by functioning as a surrogate membrane-bound receptor for the latter protein. Little is known, however, about whether Cyt1Aa can interact similarly with other Cry proteins not primarily mosquitocidal; for example, Cry2Aa, which is active against lepidopteran larvae, but essentially inactive or has very low toxicity to mosquito larvae. Here we demonstrate by ligand binding and enzyme-linked immunosorbent assays that Cyt1Aa and Cry2Aa form intermolecular complexes in vitro, and in addition show that Cyt1Aa facilitates binding of Cry2Aa throughout the midgut of C. quinquefasciatus larvae. As Cry2Aa and Cry11Aa share structural similarity in domain II, the interaction between Cyt1Aa and Cry2Aa could be a result of a similar mechanism previously proposed for Cry11Aa and Cyt1Aa. Finally, despite the observed interaction between Cry2Aa and Cyt1Aa, only a 2-fold enhancement in toxicity resulted against C. quinquefasciatus. Regardless, our results suggest that Cry2Aa could be a useful component of mosquitocidal endotoxin complements being developed for recombinant strains of B. thuringiensis subsp. israelensis and B. sphaericus aimed at improving the efficacy of commercial products and avoiding resistance.

• Applied Chemistry for Engineering
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• v.8 no.4
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• pp.610-616
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• 1997

Hepatotoxic cyanobacteria, Microcystis species, were collected from the Nakdong River and we could isolate hepatotoxins, microcystin-LR and microcystin-RR, which are also strong inhibitors of protein phosphatase 1 and 2A. From the microcystins, several microcystin derivatives were synthesized and tested on the mouse toxicity in order to establish the structure-activity relationship. Esterification od carboxyl groups of Glu and MeAsp residue produced nontoxic compounds. However, when we reduced the Mdha residue with sodium borohydride into Ala residue, toxicity was still maintained. Also, the change of guanidyl moiety of Arg residue in microcystin-LR into dimethylpyrimidyl moiety did not change the toxicity of microcystins as well. Thus the carboxyl groups seem to play important roles in binding with protein phosphatase 1 and 2A, whereas Mdha residue and the guanidyl moiety of Arg residue do not.

• Nutritional Sciences
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• v.9 no.2
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• pp.68-73
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• 2006

This study was aimed at investigating hepatic toxicity and immunomodulating effects of defatted methanol extracts of two kinds of medicinal plants, Rubus coreanus Miq. and Atractylodes japonica Koidz. in mice. Defatted methanol extracts of fruits of Rubus coreanus Miq. and rhizome of Atractylodes japonica Koidz. were added at the level of 0.5% or 5%(w/w) to cholesterol-supplemented AIN-76 diet. Each diet was fed to 8 ICR male mice for 30 days. Weight gain and food efficiency ratio of the mice fed 5.0% extract of Rubus coreanus Miq. were significantly lower than those of the mice fed 0.5% extract Relative liver weight and activity of plasma alanine aminotransfernse were significantly increased only in the mice fed 5% extract of Atractylodes japonica Koidz. compared with the others. Splenocyte proliferation was not significantly different between the groups fed 0.5% or 5.0% extract of Rubus coreanus Miq. However, splenocyte proliferation was significantly decreased in the mice fed 5.0% extract of Atractylodes japonica Koidz. compared with that in the mice fed 0.5% Production of interleukin-2 by splenocytes from the mice fed 0.5% extract of Atractylodes japonica Miq. was significantly higher than the control value and it became lower with 5.0% dietary level. Secretion of $interferon-\gamma$ was not significantly different among groups. In conclusion, the defatted methanol extract of Atractylodes japonica Koidz. was likely to exert immunomodulating effect at the level of 0.5% but it may exert adverse effects on immune and liver functions at the level of 5.0%.

• Korean Journal of Environmental Agriculture
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• v.7 no.2
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• pp.117-123
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• 1988

This study was initiated to understand the mechanism of selective toxicity of diazinon and carbofuran to killifish and loach. Conventional LC50 was calculated from fish test. IC50 with acetylcholinesterase activity was estimated using whole body and wet brain homogenate of the two fish species. Acetylcholinesterase activity of killifish was approximately twice as high as that of loach. The selective toxicity of diazinon to killifish and loach was partly (14 : 4) explained by the IC50 of diazoxon, a toxic metabolite of diazinon. IC50 of carbofuran also partly (14 : 3.4) contributed to the selectivity. These result suggested that the enzymatic method might be utilized as a screening tool for the chemicals affecting fish species of environmental concern with certain limitations which should be overcome in future studies.