A method of detecting lead was developed using square wave anodic stripping voltammetry (SWASV) with DNA-carbon nanotube paste electrode (CNTPE). The results indicated a sensitive oxidation peak current of lead on the DNA-CNTPE. The curves were obtained within a concentration range of 50 ngL-1-20 mgL-1 with preconcentration time of 100, 200, and 400 sec at the concentration of mgL-1, microgL-1, and ngL-1, respectively. The observed relative standard deviation was 0.101% (n = 12) in the lead concentration of 30.0 microgL-1 under optimum conditions. The low detection limit (S/N) was pegged at 8 ngL-1 (2.6 x10-8 M). Results showed that the developed method can be used in real-time assay in vivo without requiring any pretreatment and pharmaceutical samples, and food samples, as well as other materials requiring water source contamination analyses.
Electrodes ; Limit of Detection ; Nanotubes ; Plants* ; Water

Ginseng is a well-known traditional medicine used in Asian countries for several thousand years, and it is currently applied to medicine, cosmetics, and nutritional supplements due to its many healing and energy-giving properties. It is well demonstrated that ginsenosides, the main ingredient of ginseng, produce a variety of pharmacological and therapeutic effects on central nerve system (CNS) disorders, cardiovascular disease, endocrine secretions, aging, and immune function. Korean red ginseng extract is a dietary supplement containing ginsenoside Rb1 and ginsenoside Rg1 extracted from Panax ginseng. While the pharmacokinetics and bioavailability of the extract have been well established, its toxicological properties remain obscure. Thus, four-week oral toxicity studies in rats were conducted to investigate whether Korean red ginseng extract could have a potential toxicity to humans. The test article was administered once daily by oral gavage to four groups of male and female Sprague-Dawley (SD) rats at dose levels of 0, 500, 1,000, and 2,000 mg/kg/day for four weeks. Neither deaths nor clinical symptoms were observed in any group during the experiment. Furthermore, no abnormalities in body weight, food consumption, ophthalmology, urinalysis, hematology, serum biochemistry, gross findings, organ weights, or histopathology were revealed related to the administration of the test article in either sex of any dosed group. Therefore, a target organ was not determined in this study, and the no observed adverse effect level (NOAEL) of Korean red ginseng extract was established to be 2,000 mg/kg/day.
Aging ; Animals ; Asian Continental Ancestry Group ; Biochemistry ; Biological Availability ; Body Weight ; Cardiovascular Diseases ; Dietary Supplements ; Female ; Ginsenosides ; Hematology ; Humans ; Male ; Medicine, Traditional ; No-Observed-Adverse-Effect Level ; Ophthalmology ; Organ Size ; Panax* ; Pharmacokinetics ; Rats ; Rats, Sprague-Dawley* ; Urinalysis

Acanthopanax koreanum Nakai, a well known traditional herb grown in Jeju Island, South of Korea, has been used as a tonic and sedative agent, as well as in the treatment of diabetes and immune diseases. Mutagenicity of two lignans, syringaresinol and tortoside A isolated from A. koreanum, was assessed using Salmonella/microsome (Ames) test. Tester strains used were Salmonella typhimurium TA98, TA100, TA1535, and Escherichia coli WP2uvrA. The mutagenic activity was determined both in the absence or presence of S9 mixture. As a result, tortoside A did not cause any increase in the number of his+ revertants in S. typhimurium and E. coli WP2uvrA strains in the presence or absence of S9 mix, compared to the controls. Similarly, low concentrations of syringaresinol (750 and 1,500 microg/plate) did not show any mutagenic properties in all bacterial strains, in the presence or absence of S9 mixture. However, in the high concentration of syringaresinol (3,000 microg/plate), the number of revertants were increased in TA1535 strains, in the absence of S9 metabolic activation. Therefore, in vivo experiments such as comet assay are needed to further determine the genotoxic/carciogenic potential of syringaresinol isolated from A. koreanum.
Eleutherococcus* ; Biotransformation ; Comet Assay ; Escherichia coli ; Immune System Diseases ; Korea ; Lignans* ; Salmonella typhimurium

The silkworm extract powder contain 1-deoxynojirimycin (DNJ), a potent alpha-glycosidase inhibitor, has therapeutic potency against diabetes mellitus. Therefore, natural products containing DNJ from mulberry leaves and silkworm are consumed as health functional food. The present study was performed to evaluate the safety of the silkworm extract powder, a health food which containing the DNJ. The repeated toxicity studies and gentic toxicity studies of the silkworm extract powder were performed to obtain the data for new functional food approval in MFDS. The safety was evaluated by a single-dose oral toxicity study and a 90 day repeated-dose oral toxicity study in Sprague-Dawley rats. The silkworm extract powder was also evaluated for its mutagenic potential in a battery of genetic toxicity test: in vitro bacterial reverse mutation assay, in vitro chromosomal aberration test, and in vivo mouse bone marrow micronucleus assay. The results of the genetic toxicology assays were negative in all of the assays. The approximate lethal dose in single oral dose toxicity study was considered to be higher than 5000 mg/kg in rats. In the 90 day study, the dose levels were wet at 0, 500, 1000, 2000 mg/kg/day, and 10 animals/sex/dose were treated with oral gavage. The parameters that were monitored were clinical signs, body weights, food and water consumptions, ophthalmic examination, urinalysis, hematology, serum biochemistry, necropsy findings, organ weights, and histopathological examination. No adverse effects were observed after the 90 day administration of the silkworm extract powder. The No-Observed-Adverse-Effect-Level (NOAEL) of silkworm extract powder in the 90 day study was 2000 mg/kg/day in both sexes, and no target organ was identified.
1-Deoxynojirimycin ; Animals ; Biochemistry ; Biological Agents ; Body Weight ; Bombyx* ; Bone Marrow ; Chromosome Aberrations ; Diabetes Mellitus ; Functional Food ; Food, Organic ; Hematology ; Mice ; Micronucleus Tests ; Morus ; Mutagenicity Tests ; Organ Size ; Rats ; Rats, Sprague-Dawley ; Toxicology ; Urinalysis ; Drinking

alpha-Curcumene is one of the physiologically active components of Curcuma zedoaria, which is believed to perform anti-tumor activities, the mechanisms of which are poorly understood. In the present study, we investigated the mechanism of the apoptotic effect of alpha-curcumene on the growth of human overian cancer, SiHa cells. Upon treatment with alpha-curcumene, cell viability of SiHa cells was inhibited > 73% for 48 h incubation. alpha-Curcumene treatment showed a characteristic nucleosomal DNA fragmentation pattern and the percentage of sub-diploid cells was increased in a concentration-dependent manner, hallmark features of apoptosis. Mitochondrial cytochrome c activation and an in vitro caspase-3 activity assay demonstrated that the activation of caspases accompanies the apoptotic effect of alpha-curcumene, which mediates cell death. These results suggest that the apoptotic effect of alpha-curcumene on SiHa cells may converge caspase-3 activation through the release of mitochondrial cytochrome c.
Apoptosis ; Caspase 3 ; Caspases ; Cell Death ; Cell Survival ; Curcuma* ; Cytochromes c ; DNA Fragmentation ; Humans ; Ovarian Neoplasms*

Erythritol is a sugar alcohol that is widely used as a natural sugar substitute. Thus, the safety of its usage is very important. In the present study, short-term genotoxicity assays were conducted to evaluate the potential genotoxic effects of erythritol. According to the OECD test guidelines, the maximum test dose was 5,000 microg/plate in bacterial reverse mutation tests, 5,000 microg/ml in cell-based assays, and 5,000 mg/kg for in vivo testing. An Ames test did not reveal any positive results. No clastogenicity was observed in a chromosomal aberration test with CHL cells or an in vitro micronucleus test with L5178Y tk +/- cells. Erythritol induced a marginal increase of DNA damage at two high doses by 24 hr of exposure in a comet assay using L5178Y tk +/- cells. Additionally, in vivo micronucleus tests clearly demonstrated that oral administration of erythritol did not induce micronuclei formation of the bone marrow cells of male ICR mice. Taken together, our results indicate that erythritol is not mutagenic to bacterial cells and does not cause chromosomal damage in mammalian cells either in vitro or in vivo.
Administration, Oral ; Animals ; Bone Marrow Cells ; Chromosome Aberrations ; Comet Assay ; DNA Damage ; Erythritol* ; Humans ; Male ; Mice ; Mice, Inbred ICR ; Micronucleus Tests ; Sweetening Agents

Hypertension is a serious health problem due to high frequency and concomitant other diseases including cardiovascular and renal dysfunction. Olmesartan cilexetil is a new antihypertensive drug associated with angiotensin II receptor antagonist. This study was conducted to evaluate the mutagenicity of olmesartan cilexetil by bacterial reverse mutation test using Salmonella typhimurium (TA100, TA1535, TA98, and TA1537) and Escherichia coli (WP2 uvrA). At the concentrations of 0, 62, 185, 556, 1667, and 5000 microg/plate, olmesartan cilexetil was negative in both Salmonella typhimurium and Escherichia coli regardless of presence or absence of metabolic activation system (S9 mix). These results demonstrate that olmesartan cilexetil does not induce bacterial reverse mutation.
Biotransformation ; Escherichia coli ; Hypertension ; Imidazoles ; Receptors, Angiotensin ; Salmonella typhimurium ; Tetrazoles

The trace toxic metal copper was assayed using mercury immobilized on a carbon nanotube electrode (MCW), with a graphite counter and a reference electrode. In this study, a macro-scale convection motor was interfaced with a MCW three-electrode system, in which a handmade MCW was optimized using cyclic-and square-wave stripping voltammetry. An analytical electrolyte for tap water was used instead of an expensive acid or base ionic solution. Under these conditions, optimum parameters were 0.09 V amplitude, 40 Hz frequency, 0.01 V incremental potential, and a 60-s accumulation time. A diagnostic working curve was obtained from 50.0 to 350 microg/L. At a constant Cu(II) concentration of 10.0 microg/L, the statistical relative standard deviation was 1.78% (RSD, n = 15), the analytical accumulation time was only 60 s, and the analytical detection limit approached 4.6 microg/L (signal/noise = 3). The results were applied to non-treated drinking water. The content of the analyzed copper using 9.0 and 4.0 microg/L standards were 8.68 microg/L and 3.96 microg/L; statistical values R2 = 0.9987 and R2 = 0.9534, respectively. This method is applicable to biological diagnostics or food surveys.
Convection ; Copper ; Diagnosis ; Drinking Water* ; Drinking* ; Electrodes ; Graphite ; Limit of Detection ; Metals* ; Nanotubes, Carbon ; Organothiophosphorus Compounds ; Reference Standards ; Drinking Water

A simple and rapid liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the quantification of epsilon-acetamidocaproic acid (AACA), the primary metabolite of zinc acexamate (ZAC), in rat plasma by using normetanephrine as an internal standard. Sample preparation involved protein precipitation using methanol. Separation was achieved on a Gemini-NX C18 column (150 mm x 2.0 mm, i.d., 3 microm particle size) using a mixture of 0.1% formic acid-water : acetonitrile (80 : 20, v/v) as the mobile phase at a flow rate of 200 microl/min. Quantification was performed on a triple quadrupole mass spectrometer employing electrospray ionization and operating in multiple reaction monitoring (MRM) and positive ion mode. The total chromatographic run time was 4.0 min, and the calibration curves of AACA were linear over the concentration range of 20~5000 ng/ml in rat plasma. The coefficient of variation and relative error at four QC levels were ranged from 1.0% to 5.8% and from -8.4% to 6.6%, respectively. The present method was successfully applied for estimating the pharmacokinetic parameters of AACA following intravenous or oral administration of ZAC to rats.
6-Aminocaproic Acid ; Acetonitriles ; Administration, Oral ; Animals ; Calibration ; Mass Spectrometry* ; Methanol ; Normetanephrine ; Pharmacokinetics ; Plasma* ; Rats* ; Zinc

The anti-inflammatory effects of glycosaminoglycan (GAG) derived from Isaria sinclairii (IS) and of IS extracts were investigated in a complete Freund's adjuvant (CFA)-treated chronic arthritis rat model. Groups of rats were treated orally with 30 mg/kg one of the following: [1] saline control, extracts of [2] water-IS, [3] methanol-IS, [4] butanol-IS, [5] ethyl acetate-IS, or [6] Indomethacin(R) as the positive control for a period of two weeks. The anti-paw edema effects of the individual extracts were in the following order: water-IS ex. > methanol ex. > butanol ex. > ethyl acetate ex. The water/methanol extract from I. sinclairii remarkably inhibited UV-mediated upregulation of NF-kappaB activity in transfected HaCaT cells. GAG as a water-soluble alcohol precipitated fraction also produced a noticeable anti-edema effect. This GAG also inhibited the pro-inflammatory cytokine levels of prostaglandin E2-stimulated lipopolysaccharide in LAW 264.7 cells, cytokine TNF-alpha production in splenocytes, and atherogenesis cytokine levels of vascular endothelial growth factor (VEGF) production in HUVEC cells in a dose-dependent manner. In the histological analysis, the LV dorsal root ganglion, including the articular cartilage, and linked to the paw-treated IS GAG, was repaired against CFA-induced cartilage destruction. Combined treatment with Indomethacin(R) (5 mg/kg) and IS GAG (10 mg/kg) also more effectively inhibited CFA-induced paw edema at 3 hr, 24 hr, and 48 hr to levels comparable to the anti-inflammatory drug, indomethacin. Thus, the IS GAG described here holds great promise as an anti-inflammatory drug in the future.
Acetates ; Animals ; Arthritis* ; Atherosclerosis ; Cartilage ; Cartilage, Articular ; Edema ; Freund's Adjuvant ; Ganglia, Spinal ; Human Umbilical Vein Endothelial Cells ; Indomethacin ; Inflammation ; Jurisprudence ; Methanol ; NF-kappa B ; Rats* ; Tumor Necrosis Factor-alpha ; Up-Regulation ; Vascular Endothelial Growth Factor A