• Korean Journal of Veterinary Research
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• v.45 no.1
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• pp.29-37
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• 2005

13-week orally repeated dose toxicity was investigated to ascertain the toxic effects of Aristolochiae radix in F344 rats at dose levels of 0, 1 (0.003 AA, aristolochic acid, mg/kg), 5 (0.014 AA mg/kg), 25 (0.068 AA mg/kg), 125 (0.34 AA mg/kg), and 500mg/kg (AA 1.36 mg/kg). No mortalities were found in any of the dose groups including vehicle control groups of both sexes during the study period. Hematologic and serum biochemical examinations revealed no changes related to the test item in any of the dose groups of both sexes. However, gross findings at necropsy implicated thickening of the stomach wall. In histopathological examinations, prominent findings related to the test item treatment were observed in the stomach and urinary bladder. There were squamous cell papilloma, squamous cell hyperplasia, ulceration and erosion observed in the non-glandular stomach. Squamouse cell hyperplasia was observed at dose levels of more than 125 mg/kg in both sexes and squamous cell papilloma was observed at dose level of 500 mg/kg in both sexes. The incidence and severity of these proliferating lesions including squamous cell hyperplasia and squamous cell papilloma increased with dose dependency. Transitional cell hyperplasia was also observed in the urinary bladder at dose levels of more than 25 mg/kg in both sexes and the incidence and severity of the lesion increased with dose dependency. In conclusion, the toxic changes related to the test item treatment were observed in the stomach and urinary bladder, and the no-observed-adverse-effect level (NOAEL) was estimated to be 5 mg/kg/day for both males and females in F344 rats.

• The Korean Journal of Pain
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• v.30 no.2
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• pp.98-103
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• 2017

Background: The root of Peucedanum japonicum Thunb., a perennial herb found in Japan, the Philippines, China, and Korea, is used as an analgesic. In a previous study, sec-O-glucosylhamaudol (SOG) showed an analgesic effect. This study was performed to examine the antinociceptive effect of intrathecal SOG in the formalin test. Methods: Male Sprague-Dawley rats were implanted with an intrathecal catheter. Rats were randomly treated with a vehicle and SOG ($10{\mu}g$, $30{\mu}g$, $60{\mu}g$, and $100{\mu}g$) before formalin injection. Five percent formalin was injected into the hind-paw, and a biphasic reaction followed, consisting of flinching and licking behaviors (phase 1, 0-10 min; phase 2, 10-60 min). Naloxone was injected 10 min before administration of SOG $100{\mu}g$ to evaluate the involvement of SOG with an opioid receptor. Dose-responsiveness and ED50 values were calculated. Results: Intrathecal SOG showed a significant reduction of the flinching responses at both phases in a dose-dependent manner. Significant effects were showed from the dose of $30{\mu}g$ and maximum effects were achieved at a dose of $100{\mu}g$ in both phases. The ED50 value (95% confidence intervals) of intrathecal SOG was 30.3 $(25.8-35.5){\mu}g$ during phase 1, and 48.0 (41.4-55.7) during phase 2. The antinociceptive effects of SOG ($100{\mu}g$) were significantly reverted at both phases of the formalin test by naloxone. Conclusions: These results demonstrate that intrathecal SOG has a very strong antinociceptive effect in the formalin test and it seems the effect is related to an opioid receptor.

• Biomolecules & Therapeutics
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• v.11 no.3
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• pp.200-203
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• 2003

The present study was carried out to investigate the potential acute toxicity of bamboo leaf water extract by a single oral dose in Sprague-Dawley rats. Twenty male and female rats aged 5 weeks were randomly assigned to four groups of 5 rats each and were administered singly by gavage at dose levels of 0, 1250, 2500, or 5000 mg/kg body weight. Mortalities, clinical findings, and body weight changes were monitored for the l4-day period following the administration. At the end of 14-day observation period, all animals were sacrificed and complete gross postmortem examinations were performed. Throughout the study period, no treatment-related deaths were observed. There were no adverse effects on clinical signs, body weight, and gross finding at any dose tested. The results showed that the single oral administration of bamboo leaf water extract did not induce any toxic effect at a dose level of below 5000 mg/kg in rats and that the minimal lethal dose were considered to be over 5000 mg/kg body weight for both sexes.

• Toxicological Research
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• v.20 no.4
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• pp.325-328
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• 2004

The present study was carried out to investigate the potential acute toxicity of Balbusae caulis in taeniam by a single oral dose in Sprague-Dawley rats. Twenty rats of each sex were randomly assigned to four groups of 5 rats each and were administered singly by gavage at dose levels of 0, 1250, 2500, and 5000 mg/kg body weight. Mortalities, clinical findings, and body weight changes were monitored for the 14-day period following administration. At the end of 14-day observation period, all animals were sacrificed and complete gross postmortem examinations were per-formed. Throughout the study period, no treatment-related deaths were observed. There were no adverse effects on clinical signs, body weight, and gross finding at any dose tested. The results showed that the single oral administration of Balbusae caulis in taeniam did not cause any toxic effect at the dose levels of 5000 mg/kg or lower in rats and the minimal lethal dose was considered to be over 5000 mg/kg body weight for both sexes.

• Nutrition Research and Practice
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• v.4 no.5
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• pp.375-382
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• 2010

The precise effects of protein intake on fractional synthesis rate (FSR) of muscle protein are still under debate. The sample size of these studies was small and the conclusions in young and elderly subjects were inconsistent. To assess the effect of dietary protein intake on the FSR level, we conducted a meta-analysis of controlled protein intake trials. Random-effects models were used to calculate the weighted mean differences (WMDs). Ten studies were included and effects of short-term protein intake were evaluated. In an overall pooled estimate, protein intake significantly increased the FSR (20 trials, 368 participants; WMD: 0.025%/h; 95%CI: 0.019-0.031; P < 0.0001). Meta-regression analysis suggested that the protein dose was positively related to the effect size (regression coefficient = 0.108%/h; 95%CI: 0.035, 0.182; P = 0.009). A subgroup analysis indicated that protein intake significantly increased FSR when the protein dose was ${\leq}$ 0.80 g/kg BW (16 trials, 308 participants; WMD: 0.027%/h; 95%CI: 0.019-0.031; P < 0.0001), but did not affect FSR when the protein dose was > 0.80 g/kg BW (4 trials, 60 participants; WMD: 0.016%/h; 95%CI: 0.004-0.029; P = 0.98). In conclusion, this study is the first integrated results showing that a short-term protein intake is effective at improving the FSR of muscle protein in the healthy elderly as well as young subjects. This beneficial effect seems to be dose-dependent when the dose levels of protein range from 0.08 to 0.80 g/kg BW.

• Development and Reproduction
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• v.17 no.3
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• pp.289-297
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• 2013

Bisphenol A (BPA) is an estrogenic endocrine disrupter. However, depending on a way of treatment, the harmful effects of BPA have not been confirmed. Also, trans-generational effects of BPA on male reproduction are still controversial. Because the reabsorption of testicular fluid in the efferent ductules (ED) and initial segment (IS) is important for sperm maturation, the present study was designed to determine trans-generational effect of BPA administrated orally on expression of water transport-related molecules in the mouse ED and IS. Ethanol-dissolved BPA was diluted in water to be 100 ng (low), $10{\mu}g$ (medium), and $1mg/m{\ell}$ water (high). BPA-containing water was provided for two generations. Expression of ion transporters and water channels in the ED and IS were measured by relative real-time PCR analysis. In the ED, BPA treatment caused expressional increases of carbonic anhydrase II, cystic fibrosis transmembrane regulator, $Na^+/K^+$ ATPase ${\alpha}1$ subunit, and aquaporin (AQP) 1. No change of $Na^+/H^+$ exchange (NHE) 3 expression was detected. BPA treatment at medium dose resulted in an increase of AQP9 expression. In the IS, the highest expressional levels of all molecules tested were observed in medium-dose BPA treatment. Generally, high-dose BPA treatment resulted in a decrease or no change of gene expression. Fluctuation of NHE3 gene expression by BPA treatment at different concentrations was detected. These findings suggest that trans-generational exposure to BPA, even at low dose, could affect gene expression of water-transport related molecules. However, such effects of BPA would be differentially occurred in the ED and IS.

• The Journal of Korean Obstetrics and Gynecology
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• v.21 no.1
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• pp.55-82
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• 2008

Purpose: In this study, we evaluated anti-inflammatory activity and anti-thrombosis effect of Manbunbang(MBB) prescribed to chronic PID patients. Methods: We studied inhibitory effect of platelet aggregation, suppression effect of GPIIb/IIIa activity and inhibitory effect of $TXB_2$ and $PGE_2$ biosynthesis which were caused by ADP, epinephrine, collagen and arachidonic acid in vitro. And suppression of pulmonary embolism, changes of related factors in dextran coagulation condition model and anti-oxidative effect of oxidative damage were studied in vivo. Results: MBB extract showed LD50 of $200\;{\mu}g/ml$ or higher in mouse lung fibroblast cells, and significantly decreased the GPT and GPT level in dextran coagulation condition model compared to the control. MBB extract showed dose-dependent inhibition effect on platelet coagulation induced by ADP, epinephrine, collagen, arachidonic acid. MBB extract showed dose-dependent inhibition effect on GPIIb/IIIa activities compared to the control. MBB extract significantly suppressed TXB2 and PGE2 biosynthesis compared to the control. MBB extract suppressed pulmonary embolism triggered by collagen and epinephrine by 37.5% compared to the control. MBB extract significantly suppressed the decrease of speed of bloodstream caused by blood coagulation in dextran coagulation condition model compared to the control. Concluson : The results strongly suggest the anti-inflammatory activity of Manbunbang through anti-thrombus. Various applications using Manbunbang on inflammatory diseases are anticipated. Anti-oxidative efficacy comparison data between the Manbunbang prescription and the drug compositions may be used as important clinical information, and further investigation of anti-oxidative activities of Chrysanthemum indicum and Rhemaniae Radix should be followed.

• Biomolecules & Therapeutics
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• v.4 no.4
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• pp.354-363
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• 1996

This study was conducted to investigate the repeated dose toxicity of DA-9601, an antiulcer agent of Artemisia app. extract, in rats. DA-9601 was administered orally once a day for 4 weeks to 10 males and 10 females per group at doses of 0(vehicle control), 125, 500 or 2000 mg/kg/day. Throughout the study, no treatment-related deaths and clinical signs were observed. In female rats receiving 125 mg/kg of DA-9601, water consumption increased slightly on day 4, 11 and 25. Hematological examination showed a decrease of MCV and an increase of PLT in male rats at the doses of 500 and 2000 mg/kg groups. Blood biochemistry revealed slight decreases of cholesterol, BUN and Na in male rats and decreases of total bilirubin and creatinine and slight increases of globulin and Cl in female rats. The organ weights at the end of 4 weeks showed slight changes in some organs of treated groups. But, all these changes were not considered to be of toxicological importance, because they did not show dose-response relationship and relevance to gross and microscopic findings. Histopathologically, abnormal treatment-related changes were not observed in any organ and target organs were not detected. On the basis of these results, the NOAEL(no-observed-adverse-effect level) of DA-9601 was estimated to be more than 2000 mg/kg/day under the conditions tested.

• Toxicological Research
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• v.27 no.4
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• pp.231-240
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• 2011

Gryllus bimaculatus (Gb) was orally administered at doses of 0, 0.04, 0.2, 1 and 5 g/kg bw/day for 13 consecutive weeks. There were no observed clinical signs or deaths related to treatment in all the groups tested. Therefore, the approximate lethal oral dose of G. bimaculatus was considered to be higher than 5 g/kg in rats. Throughout the administration period, no significant changes in diet consumption, ophthalmologic findings, organ weight, clinical pathology (hematology, clinical chemistry, coagulation, and urinalysis) or gross pathology were detected. Minor changes were found in hematological parameters for the 5 g/kg Gb-treated group (triglyceride reduction of 35.8%), but all changes were within normal physiological ranges. Microscopic examination did not identify any treatment-related histopathologic changes in the organs of Gb-treated rats in the high dose group. From these results, one can conclude that the no-observed adverse effect level (NOAEL) of G. bimaculatus is higher than 5 g/kg bw/day in rats.

• Toxicological Research
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• v.20 no.3
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• pp.273-280
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• 2004

The present study was carried out to investigate the potential toxicity of dimethyl disulfide by a 2-week inhalation in F344 rats. The test article, dimethyl disulfide, was exposed by inhalation to male and female rats at dose levels of 0, 33, 100, or 300 ppm/6 hrs/day for 2 weeks. At the end of treatment period, all males and females were sacrificed. During the test period, clinical signs, mortality, body weights, food consumption, hematology, serum biochemistry, and gross findings were examined. The mean body weights of the male 300 ppm group and the female 33 ppm or higher dose groups were significantly lower than those of the control group, respectively. The mean food consumption at male 300 ppm and female 100 and 300 ppm were significantly decreased compared with the controls. Some treatment-related serum biochemical changes, including decreased alkaline phosphatase at male 300 ppm and female 100 and 300 ppm, reduced total bilirubin at male 300 ppm, and decreased alanine aminotransferase at female 300 ppm, were observed in a dose-dependent manner, but these findings were considered to be of no toxicological significance. There were no adverse effects on mortality, clinical signs, hematology, and necropsy findings in any treatment group. Based on these results, it was concluded that the 2-week repeated dose of dimethyl disulfide by inhalation resulted in suppressed body weight gain and decreased food consumption at the dose of male 300 ppm and suppressed or reduced body weight gain and decreased food consumption at the dose of female 33 ppm or higher. In the present experimental conditions, the no-observed-adverse-effect level (NOAEL) was considered to be 100 ppm/6 hrs/day for male rats and below 33 ppm/6 hrs/day for female rats.