• Toxicological Research
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• v.31 no.2
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• pp.157-163
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• 2015

Nanotechnology has advanced at an extremely rapid pace over the past several years in numerous fields of research. However, the uptake of nanoparticles (NPs) into the body after administration through various routes may pose a risk to human health. In this study, we investigated the potential ocular toxicity of 20-nm, negatively- charged zinc oxide (ZnO) NPs in rats using micro-computed tomography (micro-CT) and histopathological assessment. Animals were divided into four groups as control group, ZnO NPs treatment group (500 mg/kg/day), control recovery group, and ZnO NPs treatment and recovery group. Ocular samples were prepared from animals treated for 90 days (10 males and 10 females, respectively) and from recovery animals (5 males and 5 females, respectively) sacrificed at 14 days after final treatment and were compared to age-matched control animals. Micro-CT analyses represented the deposition and distribution of foreign materials in the eyes of rats treated with ZnO NPs, whereas control animals showed no such findings. X-ray fluorescence spectrometry and energy dispersive spectrometry showed the intraocular foreign materials as zinc in treated rats, whereas control animals showed no zinc signal. Histopathological examination revealed the retinopathy in the eyes of rats treated with ZnO NPs. Neuronal nuclei expression was decreased in neurons of the ganglion cell layer of animals treated with ZnO NPs compared to the control group. Taken together, treatment with 20-nm, negatively-charged ZnO NPs increased retinopathy, associated with local distribution of them in ocular lesions.

• Environmental Mutagens and Carcinogens
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• v.26 no.3
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• pp.63-68
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• 2006

There are $10{\sim}30%$ polyphenol and $2{\sim}4%$ caffeine in green tea. Caffeine is a kind of alkaloid containing nitrogen which cause stimulation, impatience, headache, insomnia, low birth weight infant. Because of these negative effect, decaffeined beverage came out and decaffeined coffee already have a big market since 1970s. Having proving the physiologic functions of green tea, high consumption of coffee is shifting to green tea. Because of the carcinogenic effect of the organic solvents, decaffeine processing with supercritical carbon dioxide has industrialized and have an advantage in environment-friendly and minimized flavor loss. Decaffeined green tea using supercritical carbon dioxide is considered to be safe but there are not enough study, We investigated the chromosome aberration test with mammalian cell line, CHL. When the cells were treated with 5000, 2000, 1000 ${\mu}g/ml$ and compared with the negative controls, there were no significant (P>0.05) increased chromosome aberration. Same results was observed when adding S9 mixture or not. As a result, water extract of decaffeined green tea using supercritical carbon dioxide does not induce chromosome aberration.

• Korean Journal of Pharmacognosy
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• v.38 no.3 s.150
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• pp.205-216
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• 2007

South Korea is the representative consumption country of herbal medicines and most of herbal medicines circulating in Korea have been importing from the developing countries of Southeast Asia such as China, Vietnam, Indonesia and so forth. Domestic hygiene and safety are continuously proposed because herbal medicines which are circulating have the possibility could remain contaminants or residues. Physicochemical contaminants such as heavy metals, persistent organic pollutants, radionucleosides, microbial toxins, biological contaminants such as microorganisms and animals, agrochemical residues such as pesticides, substances used for fumigation, antiviral agents, and solvent residues are classified as major contaminants and residues in herbal medicines from 2005 September WHO.$^{1)}$ Currently our administration have established a permission standard and the inspection criteria against the heavy metal, the residual pesticides and a residual sulfur dioxide. Furthermore our administration is continuously monitoring and conducting researches for the policies and their scientific ground against herbal medicines. But the appearances or discoveries of the harmful new species due to environmental and industrial developments are becoming social problems. Therefore it may be necessary to continuously consider and investigate regarding hereupon. Recently, the contamination of the mycotoxins against foods such as cereals, nuts and the powdered red pepper have developed and started became problematic issue, and possibility of contamination against the herbal medicine is proposed. And since populations who are using the herbal medicines very limited to several nations, recognition and researches about contamination of mycotoxins in herbal medicines are very insufficient. Therefore it will be need to more focus on the international regulation of quality control and safety for herbal medicines. Now on, we are going to introduce the importance, occurrence, characteristic properties, World-wide research trends and detoxification of aflatoxins, which is known as the most potent mutagen, carcinogen and teratogen mycotoxins.

• Environmental Mutagens and Carcinogens
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• v.23 no.3
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• pp.94-98
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• 2003

Quercetin and naringenin are representative flavonoids that not only exert anti estrogenic, cholesterol-lowering and antioxidant activities but also can modulate the metabolism of many xenobiotics. The activity of the specific form(s) of CYP450 is likely to be a major determinant of susceptibility to chemically induced carcinogenesis between which varies among between individuals due to different dietary habits as well as genetic characteristics. People consume cooked meat or fish together with various vegetables containing substantial amounts of quercetin and naringenin that can modify the enzyme activity of CYP1A2 to stimulate or to inhibit the mutagenic activities of HCAs. Heterocyclic amines (HCAs) produced by cooking meat products at high temperatures are promutagens that are activated by cytochrome P450 (CYP) lA2. Using a newly developed Salmonella typhimurium TA1538/1A2bc-b5 strain, we tested the effect of quercetin and naringenin on the mutagenicity of 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ). TA1538/1A2bc-b5 bears two plasmids, one expressing human CYP1A2 and NADPH-P450 reductase (NPR), and the other plasmid which expresses human cytochrome b5 (cyp b5). TA1538/1A2bc-b5 cells showed high activities of 7-ethoxyresorufin O-deethylase (EROD) and methoxyresorufin O-demethylase (MROD) associated with CYP1A2 and are very sensitive to mutagenesis induced by several HCAs. MeIQ was found to be the strongest mutagen among the HCAs tested in this system. Mutagenicity of MeIQ was enhanced 50 and 42% by quercetin at 0.1 and 1 mM, respectively, but suppressed 82% and 96% at 50 mM and 100 mM. Naringenin also increased the MeIQ-induced mutation about 37% and 22% at 0.1 and 1 mM, but suppressed it 32% and 63% at 50 mM and 100 mM concentrations, respectively, in TA 1538/1A2bc-b5 cells. Thus, they stimulated the MeIQ induced mutation at low concentrations, but strongly suppressed it at high concentrations. This biphasic effect of flavonoids was due to the stimulation or the inhibition of CYP1A2 activity in a dose-dependent manner judging by the activities of EROD or MROD in the Salmonella cells. Collectively, it is likely that the biphasic effects of quercetin and naringenin on the MeIQ-induced mutagenesis in S. typhimurium TA1538/CYP1A2bc-b5 were due to their differential modification of the CYP1A2 activity in these cells.

• Journal of the Korean Society of Food Science and Nutrition
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• v.30 no.6
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• pp.1164-1170
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• 2001

Antimutagenic and antimicrobial effects of cucumber extracts were investigated. Antimutagenic effects of cucumber extract against aflatoxin (AFB$_1$) as indirect mutagen and N-methyl-N'-nitro-N-nitrcsoguanidine (MNNG) as direct mutagen using the Ames assay system with Salmonella typhimurium TA100 were studied. 1.25~5.0% of methanol extract exhibited 11 ~ 17% of antimutagenity against AFB$_1$ and 46~85% of antimutagenity against MNNG. Among fractions of methanol extract, hexane fraction exhibited the highest antimutagenic effect against AFB$_1$ (89%) and butanol fraction exhibited the highest antimutagenic effect against MNNG (95%). Antimicrobial effects of cucumber extract were investigated on the eleven microorganisms. Methanol extract showed anitimicrobial effect on eight microorganisms. Among these tested microorganisms, Klebsiella pnemonia KCTC 2208, pseudomonas aeruginosa KCTC 2004 were the most sensitively inhibited with 13 mm clear zone on holo test. Hexane fraction showed anitimicrobial effect only on Vibrio parahaemolyticus KCTC 2471. Chloroform and ethyl acetate fractions showed a weak effect. V. parahaemolyticus showed the lowest minium inhibitory concentration (MIC) (500 ppm) among eleven tested microorganisms by methanol extract. Sterilization effect of 1% methanol extract on P. aeruginosa incubation is 10 times stronger than 0.5% methanol extract. It estimated to need 26 min for the sterilization of 90% P. aeruginosa cell counts by 1% methanol extract but 250 min by 0.5% methanol extract.

• Journal of the Korean Society of Food Science and Nutrition
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• v.21 no.2
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• pp.143-148
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• 1992

The antimutagenic effects of green-yellow vegetables toward aflatoxin B$_1$(AFB$_1$) and 4-nitroquinoline-1-ox-ide (4-NQO) using the Ames assay system with Salmonella typhimurium TA98 and TA100 were studied. Forty six to fifty percent of the methanol extracts of the vegetable samples inhibited the mutagenicity induced by AFB$_1$in TA98 and TA100. Perilla leaf, lettuce, broccoli, crown daisy, water dropwort, small water dropwort, red pepper, red pepper leaves, amaranth, spinach and radish root were significantly reduced the mutagenicity of AFB$_1$(p< 0.01). Whereas 25 out of 27 samples (93%) exhibited antimutagenicity toward a direct mutagen of 4-NQO (p< 0.01. 0.05). The samples which showed the strong antimutagenicity (>60%) were cabbage, kale, lettuce, broccoli, mustard leaf, green red pepper, green sweet pepper, spinach, amaranth, soybean sprout and immature pumpkin. The juices from the several samples also showed antimu-tagenic activity toward AFB$_1$. Cabbage, perilla leaf, small water dropwort and spinach reduced TAT100 revertants dose dependently in the range of 50-500$m\ell$/plate, however, cucumber and carrot showed little effect.

• Toxicological Research
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• v.23 no.1
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• pp.79-86
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• 2007

The isolated plantamajoside from Plantago asiatica that is often used as a marker compound in chemotaxonomic studies has various bioactivites such as the inhibitions of cyclic AMP phosphodi-esterase and 5-lipoxygenase, microbial growth and inflammation, and currently demands the generation of toxicity data. The purpose of this study was to examine the toxicities of the single and 14 days repeated dose toxicity in Sprague-Dawley rats orally administrated with plantamajoside at dose levels of 0, 500, 1000, and 2000 mg of dried material/kg body weight/day. The results showed that there was no difference in body weight change, food intake, water consumption, or relative organ weight among different dose groups. Also we observed no death and abnormal clinical signs were observed during the experimental period. Between the groups orally administered Plantago asiatica and the control group, there was no statistical significance in hematological test or serum biochemical values. There were no gross findings at final sacrifice. There was no evidence of histopathological alteration mediated by 14 days treatment with Plantago asiatica. These results suggest that no observed adverse effect level (NOAEL) of the oral application was considered to be more than 2000 mg/kg in rats under the conditions employed in this study. Another observation was performed to investigate the safety of Plantago asiatica in respect of genotoxicity. This substance was examined that Salmonella typhimurium reversion assay (Ames test) in strain TA98, TA100, TA1535. In the reverse mutation test, Plantago asiatica did not induce mutagenicity in Samonella typhimurium with and without metabolic activation. These results indicated that Plantago asiatica had no genotoxicity.

• Environmental Mutagens and Carcinogens
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• v.26 no.4
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• pp.119-124
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• 2006

There are $10{\sim}30%$ polyphenol and $2{\sim}4%$ caffeine in green tea. Caffeine is a kind of alkaloid containing nitrogen which cause stimulation, impatience, headache, insomnia, low birth weight infant. Because of these negative effect, decaffeined beverage came out and decaffeined coffee already have a big market since 1970s. Having proving the physiologic functions of green tea, high consumption of coffee is shifting to green tea. Because of the carcinogenic effect of the organic solvents, decaffeine processing with supercritical carbon dioxide has industrialized and have an advantage in environment-friendly and minimized flavor loss. Decaffeined green tea using supercritical carbon dioxide is considered to be safe but there are not enough study. We investigated the chromosome aberration test with mammalian cell line, CHL. When the cells were treated with 5000, 2000, 1000 ${\mu}g/ml$ and compared with the negative controls, there were no significant(P>0.05) increased chromosome aberration. Same results was observed when adding S9 mixture or not. As a result, water extract of decaffeined green tea using supercritical carbon dioxide does not induce chromosome aberration.

• Environmental Mutagens and Carcinogens
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• v.26 no.4
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• pp.125-132
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• 2006

Previous studies showed that epigallocatechin gallate(EGCG) have substantial effects of suppressing the N-methyl-N'-nitro-N-nitrosoguanidine(MNNG)-initiated cell transformation process on the bases of foci formation frequency and loss of anchorage dependency. In this study we tried to clarify the molecular mechanism of suppressing the cell transformation process. Mouse cell line balb/c 3T3 A31-1-1 was exposed 2 days to MNNG followed by 15 days 12-O-tetradecanoylphorbol-13-acetate(TPA) treatment for our transformation process. EGCG was added after the time point of 24 hours exposure to TPA and incubated for 19 days. 2029 genes were selected in our transformation process that showed fold change value of 1.5 or more in the microarray gene expression analysis covering the mouse full genome. These genes were found to be involved mainly in the cell cycle pathway, focal adhesion, adherens junction, TGE-$\beta$ signaling, apoptosis, lysine degradation, insulin signaling, ECM-receptor interaction. Among the genes, we focused on the 631 genes(FC>0.5) reciprocally affected by EGCG treatment. Our study suggest that EGCG down-regulate the gene expressions of up stream signaling factors such as nemo like kinase with MAPK activity and PI3-Kinase, Ras GTPase and down stream factors such as cyclin D1, D2, H, T2, cdk6.

• Toxicological Research
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• v.21 no.3
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• pp.187-193
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• 2005

The rodent Hershberger assay is considered as a potential short term in vivo screening method for the detection of androgenic or anti-androgenic compounds. The objective of this study was to evaluate the anti-androgenic activities of di(2-ethylhexyl) phthalate (DEHP), di(n-butyl) phthalate (DBP), and butylbenzyl phthalate (BBP). A 10-day Hershberger assay was performed using immature Sprague-Dawley male rats castrated at 6 weeks of age. Tastosterone propionate (TP, 0.4 mg/kg/day) was administered s.c. to castrated male rats and followed by flutamide (1, 5, 10, or 20 mg/kg/day) treatment for 10 days by oral gavage. Similarly, DEHP, DBP, or BBP were also administered by oral gavage at 250, 500, or 1000 mg/kg/day after TP (0.4 mg/kg/day) administration. As expected, flutamide significantly inhibited the TP-induced re-growth of seminal vesicles, ventral prostate, and Levator ani plus bulbocavernosus muscles (LABC) at 1 mg/kg/day and above, and Cowper's glands and glans penis at 5 mg/kg/day and above. DEHP significantly (p<0.05) decreased the seminal vesicles, ventral prostate, LABC and Cowper's glands weights at 1000 mg/kg/day. BBP at 1000 mg/kg/day significantly inhibited TP-induced re-growth of the LABC in the immature castrated male rats, whereas ventral prostate, seminal vesicles, and Cowper's glands weights were unaffected. In contrast to DEHP, DBP did not affect accessory sex organ weights at any concentration. Body weights, combined adrenal glands, and kidney weights were not affected, but liver weights were significantly increased at high dosages in the DEHP, DBP, and BBP treatment groups. Our observations strongly suggest that DEHP acts as an androgen antagonist at the high dose (i.e., 1000 mg/kg/day).