• Journal of Applied Biological Chemistry
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• v.57 no.3
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• pp.219-225
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• 2014

Azadirachta indica extract (AIE) has been regarded as a promising source of environment-friendly organic materials owing to their low mammalian toxicity. However, quite a bit of research has been reported that AIE may cause clastogens in human lymphocytes. Therefore, this study was conducted to evaluate the antimutagenic and genotoxicity of two samples of AIE. Antimutagenic test was experimented by using bacterial reverse mutation test. In the bacterial reverse mutation test, five strains Salmonella Typhimurim of two samples of AIE in order to evaluate its mutagenic potential. Bacterial reverse mutation test was also performed on positive control and negative control groups in the presence of the metabolic activation system (S-9 mix) and metabolic non-activation system. In the chromosome aberration test, Chinese hamster lung cells were exposed to AIE for 6 or 24 h with BPS, or for 6 h with S-9 mix. Negative and positive control groups were experimented for chromosome aberration test. As a result, the number of mutated colonies induced by 4-NQO were reduced by AIE treatment in all strains, indicating that AIE may have antimutagenic effects. Bacterial reverse mutation and chromosomal aberration were not shown at all concentration of AIE, regardless of activation of the metabolic system. we concluded that two AIE samples used in this study have no genotoxic effects to human, according to the genotoxicity battery system suggested by ICH (International Conference on Harmonization).

• The Korean Journal of Pesticide Science
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• v.17 no.4
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• pp.335-342
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• 2013

Sophorae radix extract (SRE) has been registered as an environment-friendly organic material that is widely used in the cultivation of crops in Korea. Matrine, the active ingredient in SRE, was reported as a toxic substance in the nervous system in mice. However, no information is available on its toxic effects in other organisms. Therefore, antimutagenicity and two kinds of genotoxicity tests (bacterial reverse mutation and chromosome aberration test) of two samples of SRE were investigated in this study. Antimutagenicity test was experimented by using bacterial reverse mutation test. In the reverse mutation test, Salmonella Typhimurim TA98, TA1535 and TA1537 were used to evaluate the mutagenic potential of SRE. Bacterial reverse mutation test was also performed on positive and negative control groups in the presence of the metabolic activation system (with S-9 mix) and metabolic non-activation system (without S-9 mix). In the chromosome aberration test, Chinese hamster lung cells were exposed to SRE for 6 or 24 hours without S-9 mix, or for 6 hours with S-9 mix. Negative and positive control groups were experimented for chromosome aberration test. As a result, the number of mutated colonies induced by 4-NQO were reduced by SRE treatment in all strains, indicating that SRE may have antimutagenic effects. Reverse mutation was not shown at all concentrations of SRE, regardless of application of the metabolic activation system. In the chromosomal aberration test, one of the SRE sample gave a suspicious positive result at 250 ${\mu}g/ml$ in the presence of S-9 mix. For the more adequate evaluation of the genotoxic potential of SRE samples, other in vivo genotoxicity study is needed.

• Archives of Pharmacal Research
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• v.19 no.4
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• pp.251-257
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• 1996

The detection of many synthetic chemicals used in industry that may pose a genetic hazard in our environment is subject of great concern at present. In this respect, the genetic toxicity of fenpropathrin ((RS)-.alpha.-cyano-3-phenoxybenzyl-2,2,3,3-tetramethyl cyclopropane carboxylate, CAS No.:39514-41-8), a pyrethroid insecticide, was evaluated in bacterial gene mutation system, chromosome aberration in mammalian cell system and in vivo micronucleus assay with rodents. In bacterial gene mutation assay, no mutagenicity of fenpropathrin (62-$5000\mug/plate$) was observed in Salmonella typhimurium TA 98, 100, 1535 and 1537 both in the absence and in the presence of S-9 metabolic activaton system. In mammalian cell system using chinese hamster lung fibroblast, no clastogenicity of fenpropathrin was also observed both in the absence and in the presence of metabolic activation system in the concentration range of $7-28\mug/ml$. And also, in vivo micronucleus assay using mouse bone marrow cells, fenpropathrin also revealed no mutagenic potential in the dose range of 27-105 mg/kg body weight of fenpropathrin (i.p.). Consequently, no mutagenic potential of fenpropathrin was observed in vitro bacterial, mammalian mutagenicity systems and in vivo micronucleus assay in the dose ranges used in this experiment.

• Toxicological Research
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• v.13 no.1_2
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• pp.95-101
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• 1997

Ethyl carbamate (EC) is a potent teratogen in rodents and is present at low concentration in fermented foods and alcohol beverages. It has been well hypothesized that some metabolic products are responsible for the teratogenic effects of the compound. In the present study, the effects of phenobarbital (PB) on EC-induced embryotoxicity were investigated in SD rats. Six groups were constructed: EC 300 (EC 300 mg/kg/day), EC 600 (EC 600 mg/kg/day), EC 600+PB (EC 600 mg/kg/day and PB 80 mg/kg/day), PB (PB 80 mg/kg/day), DR (dietary restriction, 8 g/day/rat) and a control group. Rats of the EC 600+PB group were pretreated with phenobarbital intraperitoneally for three days to induce cytochrome P450 enzymes, followed by oral administration of EC for two consecutive days. The incidence of fetal deaths in the EC 600+PB group was higher than that of the EC 600 group(42.7 vs. 14.3%). The incidence of fetal realformations in the EC 600+PB group was higher than that of the EC 600 group (external; 7.0 vs. 4.1%, visceral; 31.4 vs. 11.3%, skeletal; 11.1 vs. 6.5%). There was no embryotoxicity in the control, EC 300, PB and DR groups. These results show that the pretreatment with phenobarbital augments EC-induced embryotoxicity in rats, indicating an evidence that metabolic activation by cytochrome P450 may be the major pathway of EC to its embryotoxic forms.

• Biomedical Science Letters
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• v.16 no.3
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• pp.151-159
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• 2010

The peroxisome proliferator-activated receptor $\alpha$ (PPAR$\alpha$) is a nuclear transcription factor that plays a central role in lipid metabolism and obesity. Exercise also is a powerful modifier of the manifestations of the lipid metabolism and obesity in animal models and humans with obesity and metabolic syndrome. However, effects of exercise on lipid metabolism and obesity in normal-weight younger female subjects, having functional ovaries and not metabolic disease, remain unexplained. To explore the effects of exercise on the development of obesity and its molecular mechanism in high fat diet-fed female C57BL/6J mice, we experimented the effects of swim training on body weight, adipose tissue mass, serum lipid levels, morphological changes of adipocytes and the expression of PPAR$\alpha$ target genes involved in fat oxidation in skeletal muscle tissue of female C57BL/6J mice. Swim-trained mice had significantly decreased body weight, adipose tissue mass, serum triglycerides compared with female control mice. Histological studies showed that swim training significantly decreased the average size of adipoctyes in parametrial adipose tissue. Swim training did not affect the expression of PPAR$\alpha$ mRNA in skeletal muscle. Concomitantly, swim training did not increase mRNA levels of PPAR$\alpha$ target genes responsible for fatty acid $\beta$-oxidation, such as carnitine palmitoyltransferase 1, medium chain acyl-CoA dehydrogenase, enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase, and thiolase in skeletal muscle. In conclusion, these results indicate that swim training regulates lipid metabolism and obesity in high fat diet fed-female mice although swim training did not increase mRNA levels of PPAR$\alpha$ target genes involved in fatty acid $\beta$-oxidation in skeletal muscle, suggesting that swim training may prevent obesity and improve fitness through other mechanisms in female with ovaries, not through the activation of skeletal muscle PPAR$\alpha$.

• The Korean Journal of Physiology and Pharmacology
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• v.20 no.6
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• pp.613-619
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• 2016

Diabetic cardiomyopathy (DCM), a serious complication of diabetes mellitus, is associated with changes in myocardial structure and function. This study sought to explore the ability of insulin-like growth factor-1 (IGF-1) to modulate DCM and its related mechanisms. Twenty-four male Wistar rats were injected with streptozotocin (STZ, 60 mg/kg) to mimic diabetes mellitus. Myocardial fibrosis and apoptosis were evaluated by histopathologic analyses, and relevant proteins were analyzed by Western blotting. Inflammatory factors were assessed by ELISA. Markers of oxidative stress were tested by colorimetric analysis. Rats with DCM displayed decreased body weight, metabolic abnormalities, elevated apoptosis (as assessed by the bcl-2/bax ratio and TUNEL assays), increased fibrosis, increased markers of oxidative stress (MDA and SOD) and inflammatory factors (TNF-${\alpha}$ and IL-$1{\beta}$), and decreased phosphorylation of Akt and glycogen synthase kinase (GSK-$3{\beta}$). IGF-1 treatment, however, attenuated the metabolic abnormalities and myocardial apoptosis, interstitial fibrosis, oxidative stress and inflammation seen in diabetic rats, while also increasing the phosphorylation levels of Akt and GSK-$3{\beta}$. These findings suggest that IGF-1 ameliorates the pathophysiological progress of DCM along with an activation of the Akt/GSK-$3{\beta}$ signaling pathway. Our findings suggest that IGF-1 could be a potential therapeutic choice for controlling DCM.

• Environmental Mutagens and Carcinogens
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• v.16 no.1
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• pp.6-12
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• 1996

To investigate the clastogenicity of taxol and its precursor, 10-aleacetyl baccatin III, we performed chromosomal aberration assay with chinese hamster lung cells in vitro. The IC$_{50}$ values of taxol and 10-deacetyl baccatin III were determined as $1/16 \times 10^{-4}$ M (5.34 $\mu$g/ml) and $1 \times 10^{-2}$ M (560 $\mu$g/ml) in MTT assay, respectively. It means that the cytotoxicity of taxol revealed 100 times more cytotoxic than 10-deacetyl baccatin III in chinese hamster lung cell line. Nevertheless the strong positive genetic toxicity of taxol in the bone marrow micronucleus assay in vivo which was recently reported, we observed weak positive clastogenicity of taxoi only in the absence of metabolic activation system in the concentration ranges used in this experiment. Moreover, to clarify the involvement of metabolic fate of taxol because of its strong positive result in vivo, 10-deacetyl baccatin III which is a precursor in taxol synthesis, also subjected in chromosomal aberration assay in vitro. However, we observed no clastogenicity of 10-deacetyl baccatin III in this experiment. From above results, it was suggested that the esterification at C-13 appears to be relative for its genetic toxicity in chromosome aberration using chinese hamster lung cell in vitro.

• Applied Biological Chemistry
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• v.3
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• pp.1-7
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• 1962

In order to study the rate control step in the protein metabolic course of the chlorophyll formation, the transaminase activities which are obtained freely in the extracts of cotyledons of germinating peas at the light and the dark places, are measured in Beckman mopel D.U, spectrophoto meter at 490 mu. In this case, of two enzymatic reaction products; oxalacetic acid and pyruvic acid, the former is converted to pyruvic acid by aniline citrate and after each pyruvate phenyl hydrazones are extracted by toluenes: when this is treated with strong alcoholic alkali, a colored hydrazone is formed and it is measured by above apparatus. The estimated G.O.T. and G.P.T. in the germinated cotyledons at dark and light places considerably differ in their activities; G.O.T. and G.P.T. activities which are formed at the light are more increased than at the dark and also they differ in their rates through germination, though G.O.T. activity increment is smoothly but that of G.P.T. is more sharply, and they are considered to be directly affected to the chlorophyll formation and indirectly to the growth. G.O.T. and G.P.T. in each fractions of cell in the cotyledons should be formed by dissociation of zymogens in the microsomal fractions and it seems to promoted by light. In the formation of the chlorophyll, the protein metabolism occurred mainly in the microsomal fractions and the rate determining step is found at the point where the zymogene that is able to produce G.P.T. is activated, and this activation is promoted by light as noted above.

• Nutrition Research and Practice
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• v.12 no.2
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• pp.110-117
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• 2018

BACKGROUND/OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disease and is closely associated with metabolic syndrome. In the present study, we observed the effect of ethanol extract of Allium fistulosum (EAF) on NAFLD and have suggested the possibility of using EAF as a natural product for application in the development of a treatment for NAFLD. MATERIALS/METHODS: The preventive effect on hepatic lipid accumulation was estimated by using an oleic acid (OA)-induced NAFLD model in vitro and a Western diet (high-fat high-sucrose; WD)-induced obese mouse model. Animals were divided into three groups (n = 7): normal diet group (ND), WD group, and WD plus 1% EAF group. RESULTS: EAF reduced OA-stimulated lipid accumulation in HepG2 cells in the absence of cellular cytotoxicity and significantly blocked transcriptional activation of sterol regulatory element-binding protein 1 and fatty acid synthase genes. Subsequently, we investigated these effects in vivo in mice fed either ND or WD in the presence or absence of EAF supplementation. In comparison to the ND controls, the WD-fed mice exhibited increases in body weight, liver weight, epididymal fat weight, and accumulation of fat in hepatocytes, and these effects were significantly attenuated by EAF supplementation. CONCLUSIONS: Allium fistulosum attenuates the development of NAFLD, and EAF elicits anti-lipogenic activity in liver. Therefore, EAF represents a promising candidate for use in the development of novel therapeutic drugs or drug combinations for the prevention and treatment of NAFLD.

• Toxicological Research
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• v.30 no.3
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• pp.211-220
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• 2014

Resveratrol has received considerable attention as a polyphenol with various biological effects such as anti-inflammatory, anti-oxidant, anti-mutagenic, anti-carcinogenic, and cardioprotective properties. As part of the overall safety assessment of HS-1793, a novel resveratrol analogue free from the restriction of metabolic instability and the high dose requirement of resveratrol, we assessed genotoxicity in three in vitro assays: a bacterial mutation assay, a comet assay, and a chromosomal aberration assay. In the bacterial reverse mutation assay, HS-1793 did not increase revertant colony numbers in S. typhimurium strains (TA98, TA100, TA1535 and TA1537) or an E. coli strain (WP2 uvrA) regardless of metabolic activation. HS-1793 showed no evidence of genotoxic activity such as DNA damage on L5178Y $Tk^{+/-}$ mouse lymphoma cells with or without the S9 mix in the in vitro comet assay. No statistically significant differences in the incidence of chromosomal aberrations following HS-1793 treatment was observed on Chinese hamster lung cells exposed with or without the S9 mix. These results provide additional evidence that HS-1793 is non-genotoxic at the dose tested in three standard tests and further supports the generally recognized as safe determination of HS-1793 during early drug development.