• Korean Journal of Veterinary Service
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• v.38 no.3
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• pp.173-180
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• 2015

Environmental pesticides used for insect control can be transferred from plants to animals even to livestock animals through food chain. Human beings also can be exposed to pesticides by consuming polluted dairy products, including meats, eggs and other milk products. Therefore, the Ministry of Food and Drug Safety (MFDS) established Standard for Pesticide Residue Limits in dairy products. The QuEChERS (quick, easy, cheap, effective, rugged and safe) methods for detecting residual pesticides are relatively well established for fruits and vegetables, however, the methods for meat have not been appropriately studied yet. In the present work, pyraclofos was used as an organophosphate pesticide to examine its tissue residue in experimental animals by QuEChERS methods. For this, pyraclofos (150 mg/kg body weight) was orally administered to male rats once a day for 2 days. After 6, 12, and 24 hr of the treatment, the tissue residues in liver and femoral muscle of the rats were determined using QuEChERS methods followed by HPLC analyses. In preliminary studies, the recovery rates of spiking samples of pyraclofos demonstrated approximately 109~110% from the tissues. In previous study, pyraclofos tissue residues were observed with significantly high levels in livers and muscles at 6 hr of oral treatment. Then, they were almost completely disappeared after 24 hr of the administration, indicating the orally exposed pyraclofos is rapidly absorbed and distributed to body organs, then quickly excreted from the body with a negligible level of tissue residue. The alterations in blood chemistry as well as the histopathology of heart, lung, liver, spleen and kidney have also been investigated in the experimental animals for assessing acute toxic effects of pyraclofos. The obtained blood chemistry indexes (ALT and AST) showed maximum peak values at 12 hr after the oral administration and decreased to the normal levels at 24 hr of the treatment. Histopathologic observation exhibited acute hepatic damages at 24 hr of the treatment. In conclusion, we suggest that QuEChERS method can be adequately optimized for the analysis of pyraclofos residues in animal tissues.

• The Journal of Korean Medicine
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• v.34 no.3
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• pp.69-85
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• 2013

Objectives: This study investigated the anti-osteoarthritic effects of Kyejiinsam-tang (hereinafter referred to KIT) on the monosodium iodoacetate (MIA)-induced osteoarthritis rats. Methods: Anti-oxidative effects of KIT were measured by scavenging activities of DPPH, reactive oxygen species (ROS) and nitric oxide (NO). Scavenging activities of anti-oxidation in lipopolysaccharide (LPS)-treated RAW 264.7 cells were also measured for inhibitory effects against the production of inflammatory mediators (tumor necrosis factor-${\alpha}$, interleukin-$1{\beta}$, interleukin-6). Osteoarthritis was induced in rats by injecting MIA in the knee joint. Rats were divided into a total of 4 groups (n=6). The normal group were not treated at all without inducing osteoarthritis whereas the control group were induced for osteoarthritis by MIA and oral medicated physiological saline per day. The positive comparison group was injected with MIA and after 7 days, 2 mg/kg of Indomethacin. The experimental group was injected with MIA and after 7 days was medicated with 34 mg/kg of KIT. Indomethacin and KIT were orally-medicated for each substance a total of 4 weeks, once per day. Weight-bearing on hind legs was measured every week after MIA injection. At the end of the experiment (5 weeks after MIA injection), micro CT (computed tomography)-arthrography and histopathological examinations on the articular structures of knee joint were performed. The effect on inflammatory cytokines and immunological cells in synovial fluid was measured. Volume of cartilage was measured by micro CT-arthrography. Injury to synovial tissue was measured by H & E (hematoxylin and eosin), Safranin-O immunofluorescence. Results: 1. Cytotoxicity against hFCs was insignificant. 2. KIT showed the potent full term for DPPH. 1. NO was significantly reduced by KIT (at 100, $200{\mu}g/m{\ell}$) and ROS was also reduced, but not significantly, by KIT (at $200{\mu}g/m{\ell}$). 2. IL-6 and IL-$1{\beta}$ were significantly reduced by KIT (at 100, $200{\mu}g/m{\ell}$) and TNF-${\alpha}$ was also reduced, but not significantly, by KIT (at $200{\mu}g/m{\ell}$). 1. In hind legs weight-bearing measurement, level of weight increased. 2. Functions of liver and kidney were not affected. 3. IL-$1{\beta}$ was significantly reduced and TNF-${\alpha}$, IL-6 were also reduced but not significantly. 4. PGE2 (prostaglandin E2), LTB4 (leukotriene B4) were significantly reduced in the KIT group. 5. MMP-9 (matrix metalloproteinase-9), TIMP-1 (tissue inhibitor of metalloproteinases-1) and Osteocalcin were significantly reduced in the KIT group. 6. Destruction of cartilage on micro CT arthrography was reduced but had no significant differences. 7. Histopathologically, injury to synovial membrane of the KIT group was decreased and proteoglycan content of KIT group was increased. Conclusions: According to this study, Kyejiinsam-tang has inhibiting effect on the progression of arthritis in MIA-induced osteoarthritis rat. Kyejiinsam-tang has anti-oxidants and anti-inflammation effects, and is related to inhibiting the activity of inflammatory cytokine and injury of volume in cartilage.

• Toxicological Research
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• v.14 no.3
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• pp.293-300
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• 1998

Previous studies have shown that the heterocycles including thiazoles are efficacious in inducing phase phase II metabolizing enzyme as well as certain cytochrome P450s and that the inductin of these matabolizing enzymes by the heterocyclic agents is highly associated with their hepatotoxicity. In the present study, the effects of benzylisothiazole (BIT), which has a isothiazole moiety, on the expression of microsomal epoxide hydrolase (mEH), major glutathione S-transerases and cytochrome P450s were studied in the rat liver in association with its hepatotoxicity. Treatment of rats with BIT(1.17 mmol/kg, 1~3d) resulted in substantial increases in the mEH. rGSTA2, rGSTA2, rGSTM1 and rGSTM2 mRNA levels, whereas rGSTA3 and rGSTA5 mRNA levels were increased to much lesser extents. A time-course study showed that the mRNA levels of mEH and rGSTs were greater at 24hr after treatment than those after 3 days of consecutive treatment. Relative changes in mEH and rGST mRNA levels were consistent with those in the proteins, as assessed by Western immunoblot analysis. Hepatic cytochrom P450 levels were monitored after BIT treatment under the assumption that metabolic activation of BIT may affect expression of the enzymes in conjunction with hepatotoxicity. Immunoblot analysis revealed that cytochrome P450 2B1/2 were 3-to 4-fold induced in rats teatd with BIT(1.17 mmol/kg/day.3days), whereas P450 1A2, 2C11 and 3A1/2 levels were decreased to 20~30% of those in unteatd rats. P450 2E1 was only slightly decreased by BIT. Thus, the levels of several cytochrome P450s were suppressed by BIT treatment. Rats treated with BIT at the dose of 1.17mmol/kg for 3 days exhibited extensive multifocal nodular necrosis with moderate to extensive diffuse liver cell degeneration. No notable toxicity was observed in the kidney. These results showed that BIT induces mEH and rGSTs in the liver with increases in the mRNA levels, whereas the agent significantly decreased major cytochrome P450s. The changes in the detoxifying enzymes might be associated with the necrotic liver after consecutive treatment.

• The Korean Journal of Pesticide Science
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• v.11 no.4
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• pp.222-229
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• 2007

It is well known the functional foods are very useful to prevent serious diseases and promote health. Therefore, they are often called as nutraceuticals, designer foods, and pharmafoods, etc. Most of foods have diverse functions because they provide nutrients, energies and fibrinoid materials. When foods are taken in the body, they promote the biological defense system against diseases through the supply of the essential or healthy materials to human being's organs. The mode of action and functional foods in human body have not been clarified yet. Antioxidant is known as one of the therapeutic aids which can be reduced pesticide poisoning. Onion has a strong antioxidant effect. This study was carried out to elucidate an antioxidant function of onion by determination of superoxide dismutase in liver, lung, serum of male rat administered by intraperitonial injection of 0, 2, $4\;mg\;kg^{-1}$ cblorpyrifos after administrated orally with onion for 6 weeks. Damage of liver and kidney was also investigated by biochemical analysis of serum(AST, ALT, BUN/Creatine ratio). SOD(superoxide dismutase) activity of onion-administrated group is higher than control group. In liver and lung, SOD activity of onion+cblorpyrifos administrated group is higher than only chlorpyrifos administrated group. BUN/Creatinine ratio of onion+chlorpyrifos administrated group was decreased compared with only chlorpyrifos-administrated group.

• Journal of Nutrition and Health
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• v.38 no.5
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• pp.352-363
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• 2005

The previous extensive in vitro studies on the antioxidative activities of a number of Korean grains, vegetables, seaweeds and mushrooms, and the various combinations of these food source exhibited a wide range of antioxidative activities, and four food mixtures composed of 5 kinds of foods (5A, 5B, 5C and 5D) were designed from 16 selective foods showing. high antioxidant effect, in vitro, to find the good combinations for the meal planning. Mixture 5B or 5C contained very high levels of total flavonoid and polyphenol, and ethanol extract from 5A, 5B or 5C showed very strong inhibitory effects against in vitro $Fe^{2+}-induced$ lipid peroxidation and ethanol extract from 5B or 5C showed remarkable DPPH radical scavenging effect and lipid peroxide-protein conjugation inhibition effect. And in vivo study was also carried out with two mixtures (5B, 5C). Powders (P5B, P5C) or ethanol extracts (E5B, E5C) of these mixtures were supplemented to Sprague-Dawley rats fed on high fat $(15\%)-high$ cholesterol $(1\%)$ semipurified diet for 5 weeks. The total antioxidant power in serum was significantly higher in P5B, P5C, E5B and E5C groups than in high fat control group, and $ascorbate-Fe^{2+}-induced$ TBARS was significantly lowered by E5B supplementation in rat liver. In liver tissue, Cu, Zn-SOD activity was significantly higher in P5B and E5B groups than in high fat control group, while catalase or GSH-peroxidase (GPx) activity was not changed by any supplementations. In kidney, Cu, Zn­SOD activity was significantly higher in P5B group than in high fat control group, while GPx activity was not changed by any supplementations. Taken together, mixture 5B and 5C showed very strong antioxidative effects both in vitro and in vivo. Therefore, the ingredient Korean foods of 5B and 5C could be recommended to take a lot together for prevention from age-related chronic diseases.

• Clinical and Experimental Reproductive Medicine
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• v.32 no.4
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• pp.301-314
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• 2005

Objective: Rebamipide is a propionic acid derivative that has an action of the inhibition of superoxide production and removal of hydroxyl radical with the sperm incubation and cryopreservation. In the present study, to investigate whether rebamipide is useful to treat male infertility and sterility, the author observed the antioxidative effects in patient with male infertility and also examined its absorption and distribution in rat genital organ. Methods: To measure the distribution of rebamipide in reproductive organ in the rat, carbon indicated rebamipide, $^{14}C-OPC-12759$, was orally administered to 10 Spraque-Dawley rats and its organ concentration in serum, liver, kidney, stomach, duodenum, colon, urinary bladder, seminal vesicle, epididymis and testicle were measured each time after 0.5, 1, 2, 4, 8 and 24 hours by using HPLC fluorescent method. The concentrations in semen were measured by HPLC fluorescent method in a sample of 50 infertile males who took 900 mg of rebamipide daily for 3 months. To measure the antioxidative effect and fertility rate for 3 months, each month before and after the treatment, sperm motility, vitality, the oxygen free radical formation, level of peroxidation, fetilizing capacity of semen sample which were obtained from infertile male patients by masturbation after at least 48 hours abstinence were analyzed by computer assisted semen analyzer, eosin-nigrosin stain, chemiluminescence, thiobarbituric acid method and hypo-osmotic swelling test. Simultaneously in a sample that wanted baby, both pregnancy and delivery were researched. Results: The $^{14}C-OPC-12759$ concentration in the body of white rats was highest in gastrointestinal organ like stomach, smal intestine and duodenum and followed by genital organ like seminal vesicle, testis and epididymis. The rebamipide concentration in semen of infertile males was $220.77{\pm}327.84ng/mL$ (SD) which showed a large deviation but it was higher than serum which was $126{\pm}76ng/mL$ (SD). In the infertile males, after the treatment with rebamipide, the level of seminal reactive oxygen species (ROS) and lipid peroxidation have significantly decreased in duration of the treatment (p<0.05) and sperm vitality and fertilizing capacity except sperm motility significantly improved on post treatment of 2~3 months (p<0.05). Out of the 41 cases who hoped for pregnancy, 15 cases (36.6%) became pregnant and 12 cases had childbrith, 2 cases had miscarriage and one case is ongoing. The side effect was observed in 1 case (2%) which experienced diarrhea but it was lost spontaneously. Conclusions: We conclude from this study that rebamipide showed relatively high tendancy of absorption and excretion in the genital organ. In infertile males who had elevated ROS in semen, by specifically inhibiting the cell damage from the antioxidation, a way to preserve sperm motility, vitality and fertilizing capacity was confirmed.

• Journal of Korean Society of Occupational and Environmental Hygiene
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• v.16 no.3
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• pp.233-244
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• 2006

Of many volatile organic detergents for metals, benzine(CAS No. 8030-30-6), of which the toxicity has not yet been proven, has been used as an alternative of the halide compounds in the consideration of toxic effects, global warming and the destruction of ozone layer. In order to evaluate the effects of the benzine on human body by investigating the subchronic inhalation toxicity, to obtain the basic data for establishing the criteria of exposure in working environments and to classify the hazardousness in compliance with the Industrial Safety and Health Act by evaluating the hazardousness, repeated inhalation exposure test was carried with SD rats. The rats were grouped by 10 females and males each. The repetitive inhalation exposures were carried out at 4 levels of concentration of 0 ppm, 60 ppm, 300 ppm, and 1,500 ppm, for 6 hours a day, 5 days a week, for 13 weeks. The results are described hereunder. 1. No death of the animals of the exposed and controlled groups in the test period. Not any specific clinical symptoms, change in feed intake quantity, abnormality in eye test, or change in activity were observed. 2. In the 300 ppm and 1,500 ppm groups, weight reduction in the female groups and weight increase of liver and kidney in the male groups compared with control group were observed with statistical significance(p<0.05). 3. In the blood test, the HCT increased in the male 300 ppm group and the number of hematocyte increased, MCV and MCH decreased in the male 1,500 ppm group. In the female 1,500 ppm group, the HB decreased and the distribution width of the hematocyte particle size increased. In the blood biochemistry test, the TP in the male 1,500 ppm group and the LDH in the female 1,500 ppm group were increased with statistical significance(p<0.05). 4. Under the test conditions of the present study with SD rats, the NOEL was evaluated to be from 60 ppm to 300 ppm for both male and female groups. By extrapolation, the NOEL for human who work 8 hours a day was evaluated to be from 128 ppm to 640 ppm 5. Since the NOEL evaluated in this study do not exceed 60ppm(0.184 mg/L) the test material does not belong to the classification of the hazardous substance "NOEL${\leq}$0.5mg/L/6hr/90day(rat), for continuous inhalation of 6hours a day for 90 days" nor to the basic hazardous chemical substance class 1(0.2 mg/L/6hr/90day(rat) defined by the GHS which is a criteria of classification and identification of chemical compounds. However, considering the boiling point($30-204^{\circ}C$), flashing point($-40^{\circ}C$), vapor pressure(40 mmHg), and the inflammable range(1.0 - 6.0 %), sufficient care should be taken for handling in the safety aspects including fire or explosion.

• Journal of the Korean Society of Food Science and Nutrition
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• v.25 no.6
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• pp.1016-1023
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• 1996

The effect of dietary calcium levels, 50%, 100%, and 200% of requirement, on iron utilization was evaluated in 30 Sprague-Dawley female rats by use of balance study for 3 weeks. In the results of this study, there were no significant difference in feed intake, body weight gain, hemoglobin level, hematocrit, calcium and iron levels in serum and tissues across the groups supplemented different calcium levels. Calcium content in kidney of high-calcium group was significantly higher than that of other groups. Urinary and fecal calcium excretions increased as the level of dietary calcium was increased. With increasing levels of dietary calcium, daily calcium retention was accelerated, but daily calcium retention rate was diminished. Iron intake was significantly higher in adequate-calcium group than that in low-calcium or high-calcium group. Urinary and fecal iron excretions were significantly lower in low-calcium group than those in adequate-calcium or high-calcium group. Apparent retention and retention rate estimated by intake, urinary and fecal excretions of iron were significantly lower in high-calcium group t]lan those in low-calcium or adequate-calcium group. These results suggest that taking dietary calcium supplements reduce the absorption of dietary iron.

• Journal of Korean Medicine Rehabilitation
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• v.25 no.3
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• pp.1-9
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• 2015

Objectives To evaluate Shinbaro Pharmacopuncture safety through analysis of potential single-dose intramuscular toxicity of Sinbaro Pharmacopucture in SD rats and Beagle dogs. Methods Single-dose intramuscular toxicity of Shinbaro Pharmacopuncture was assessed in accordance with Korea Food and Drug Administration Guidelines for toxicity testing of Medicinal Products. The SD rats were treated intramuscularly with Shinbaro Pharmacopuncture at doses of 0, 4.6, 9.2, and 18.5 mg/kg, respectively. The Beagle dogs were treated intramuscularly with Shinbaro Pharmacopuncture at doses of 2.3, and 4.6 mg/kg, respectively, and after 3 days, the procedure was repeated a second time at doses of 0.6, and 1.2 mg/kg, respectively, for toxicity testing. Mortality, change in body weight, and necropsy findings were examined for the study period. Results There were no mortalities, general symptoms, or body weight changes in the SD rats. While pyelectasis of the left kidney was observed in a male rat in the 4.6 mg/kg administration group, natural occurrence is common, and does not appear to be related with the test substance. No mortalities were observed in the Beagle dogs. In assessment of general symptoms, a female dog in the 9.2 mg/kg group displayed body weight decrease due to leftover food, but the change in body weight was within the normal range seen at 6~7 months, and the necropsy findings were not significant. The toxicity of the test substance appears to be minimal. Conclusions The results suggest that the lethal dose 50 ($LD_{50}$) and approximate lethaldose (ALD) value in single intramuscular administration of Shinbaro Pharmacopuncture in SD rats and Beagle dogs are higher than 18.5 mg/kg.

• Journal of the Korean Society of Food Science and Nutrition
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• v.37 no.9
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• pp.1120-1125
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• 2008

This study was carried out to investigate the effects of Sophorae fructus extracts on antioxidative potential, free radical generation and the lipid levels in rats. Sprague-Dawley (SD) rats were divided into 2 groups of either AIN-76 diet (control group) or modified AIN-76 diet with 0.5% Sophorae fructus extracts for 4 weeks. The result were as follows: body weight gain and feed efficiency ratios were not significantly different in both groups. Antioxidative potentials were significantly increased in the group fed Sophorae fructus extracts compared to control group; however, there was no difference in free radical generation. Organ (heart, kidney, liver, spleen) weights in rats were not different in both groups. Total cholesterol level in Sophorae fructus group was significantly decreased compared to control group. Serum HDL-cholesterol level in Sophorae fructus group was significantly higher than control group. Serum phospholipid and triglyceride contents in Sophorae fructus group were no different from control group. These results suggest that supplementation of Sophorae fructus extracts may beneficially contribute to the effects of antioxidative potential and lipid levels in rats.