• Fisheries and Aquatic Sciences
• /
• v.13 no.1
• /
• pp.71-78
• /
• 2010

We investigated the effect of Cu exposure on the activities of protective antioxidant enzymes in the gills and digestive glands of the manila clam Ruditapes phillippinarum exposed to subchronic concentrations (0, 20, 40, and $80{\mu}gL^{-1}$) of waterborne Cu. No mortality occurred during the experimental period, and no significant condition index differences were observed in any exposure group compared with the control. No significant differences were observed in the digestive glands and gills of the clams observed during 15 days of exposure, but after 30 days, the SOD activity in the gill showed a significant difference between the $80{\mu}gL^{-1}$ Cu-exposed group and the control. GPx activities in the digestive glands and gills were significantly lower after 30 days of Cu exposure. Gill GR activity in the high-exposure group ($80{\mu}gL^{-1}$) was significantly elevated compared with that in the control group. GST activities in the digestive glands of all groups did not change over 30 days. However, GST activity in the gill at $80{\mu}gL^{-1}$ Cu was significantly higher after 15 and 30 days of exposure. GSH activities in the gill showed patterns similar to those of GST activities during exposure periods. In the digestive glands, GSH activity was higher only at $80{\mu}gL^{-1}$ after 30 days exposure. In digestive glands and gills, the MDA levels of clams exposed to $80{\mu}gL^{-1}$ Cu were significantly higher after 30 days of exposure.

• Archives of Pharmacal Research
• /
• v.19 no.5
• /
• pp.390-395
• /
• 1996

To investigate whether $AT_{1}$ receptor antagonists are acting by increasing endothelium-de-pendent and -independent relaxation of aortas in normotensive rats, $AT_{1}$ receptor antagonists, losartan and KR-30988, and angiotensin converting enzyme inhibitor, captopril, were orally administered for two weeks (50 mg/kg, b.i.d.). THe blood pressure, heart rate and body weight were not significantly changed by losartan, KR-30988 and captopril compared to the control group. In aortic preparations, the $pD_{2}$ of KR-30988 for ACh-induced relaxation was 8.33 $\pm$ 0.16, significantly (p <0.05) lower than that of control group $(7.71 \pm 0.15)$. ACh-induced relaxation was significantly increased on losartan-treated group (p<0.01) at $10^{-6}$ M of ACh, and in captopril-treated group (p<0.05) at the range of $10^{-7}$ -$10^{-5}$ M of ACh. The $pD_{2}$ values for histamine-induced relaxatio of losartan, KR-30988 and captopril were 5.57 $\pm$ 0.10, 5.85 $\pm$ 0.21 and 5.60 $\pm$ 0.01, respectively, with significant differences in all groups (p<0.01) compared to that of control group (5.13 $\pm$ 0.09). ACh-induced relaxations of aortic preparations were not changed by pretreatment of indomethacin ($10_{-5}$ M), and completely bolcked by pretreatment of L-NAME $(10_{-5}M)$ in all groups. Sodium nitroprusside-induced relaxations were not significantly changed by all drugs tested in this experiments. These results suggest that $AT_{1}$ receptor antagonists, losartan and KR-30988, enhance the endothelium-dependent relaxatio on aortic preparations through the release of, or increase sensitivity, to nitric oxide in nor-motensive rats.

• Journal of Pharmacopuncture
• /
• v.19 no.3
• /
• pp.213-224
• /
• 2016

Objectives: Ginseng Rh2+ is enzyme-treated ginseng extract containing high amounts of converted ginsenosides, such as compound k, Rh2, Rg3, which have potent anticancer activity. We conducted general and genetic toxicity tests to evaluate the safety of ginseng Rh2+. Methods: An acute oral toxicity test was performed at a high-level dose of 4,000 mg/kg/day in Sprague-Dawley (SD) rats. A 14-day range-finding study was also conducted to set dose levels for the 90-day study. A subchronic 90-day toxicity study was performed at dose levels of 1,000 and 2,000 mg/kg/day to investigate the no-observed-adverse-effect level (NOAEL) of ginseng Rh2+ and target organs. To identify the mutagenic potential of ginseng Rh2+, we conducted a bacterial reverse mutation test (Ames test) using amino-acid-requiring strains of Salmonella typhimurium and Escherichia coli (E. coli), a chromosome aberration test with Chinese hamster lung (CHL) cells, and an in vivo micronucleus test using ICR mice bone marrow as recommended by the Korean Ministry of Food and Drug Safety. Results: According to the results of the acute oral toxicity study, the approximate lethal dose (ALD) of ginseng Rh2+ was estimated to be higher than 4,000 mg/kg. For the 90-day study, no toxicological effect of ginseng Rh2+ was observed in body-weight changes, food consumption, clinical signs, organ weights, histopathology, ophthalmology, and clinical pathology. The NOAEL of ginseng Rh2+ was established to be 2,000 mg/kg/day, and no target organ was found in this test. In addition, no evidence of mutagenicity was found either on the in vitro genotoxicity tests, including the Ames test and the chromosome aberration test, or on the in vivo in mice bone marrow micronucleus test. Conclusion: On the basis of our findings, ginseng Rh2+ is a non-toxic material with no genotoxicity. We expect that ginseng Rh2+ may be used as a novel adjuvant anticancer agent that is safe for long-term administration.

• Development and Reproduction
• /
• v.24 no.3
• /
• pp.159-165
• /
• 2020

Previously, we reported adverse effects of low-dose nonylphenol (NP) exposure on the reproductive parameters of F1 female mice. In the present study we further investigated the pathohistological effect of NP exposure on the reproductive organs in F1 female mice. NP exposures were continuously conducted from parental pre-mating period until the postnatal day (PND) 33 of F1 offspring for vaginal examination. Mice were sacrificed on PND 30 and the reproductive tissue weights were measured. The initial (at PND 21) body weights of the NP-50 group animals were significantly lower than those of control group animals, and the weight deficit were recovered when the terminal (PND 33) body weights were measured. Early vaginal opening was found in NP group animals (p<0.05). Pathohistological studies revealed that NP-treated F1 animals showed prominent increase in the ovarian follicle numbers (p<0.01), and decrease in the diameter of uterine myometrium (p<0.01), and increase in the diameter of luminal epithelium (p<0.05). The present study demonstrated that the subchronic low-dose NP exposure induced early beginning of puberty and pathohistological abnormalities in ovary and uterus of F1 mice. Further studies are needed to achieve a better understanding on the action mechanism of NP in pubertal onset and to find a way to avoid a hazardous situation provoked by NP exposure.

• Journal of Korean Society of Occupational and Environmental Hygiene
• /
• v.21 no.2
• /
• pp.73-81
• /
• 2011

The purpose of this study was to obtain scientific information regarding classification and health hazards that may result from a 13 weeks inhalation exposure of isoprene in Sprague-Dawley (SD) rats. The testing method was conducted in accordance with OECD guidelines for the testing of chemicals No. 413. The Rats were divided into 4 groups (10 male and 10 female rats in each group) and exposed to 0, 360, 1,620, 7,300 ppm isoprene in each exposure chamber for 6 h/day, 5 days/week, for 13 weeks. As a result, there were no mortality or abnormality during the period of study and did not show any significant changes of body weight. There were no dose response changes in urinalysis, hematological and serum biochemical value examination. Relative organ weight was increased significantly the right kidney in 7,300 ppm group of male rats. In female rats, relative organ weight of the left kidney and the both lungs in 1,620 ppm group and the left lung and the both kidneys in 7,300 ppm group were increased significantly. But the histopathological findings did not reveal any exposure-related changes. According to the above results, the no observable adverse effect level (NOAEL) of isoprene was 7,300 ppm (20.3 mg/L) in both male and female rats. In conclusion, Isoprene was not classified specific target organ toxicity of the 'Standard for Classification and Labeling of Chemical Substance and Material Safety Data Sheet' (Ministry of Employment and Labor, 2009).

• Development and Reproduction
• /
• v.23 no.3
• /
• pp.255-262
• /
• 2019

Previously, we reported negative effects of low-dose nonylphenol (NP) exposure on the reproductive organs of F1 male mice. In the present study was further investigated the endocrine disrupting effect of NP exposure to F2 generation male mice. Mice were divided into 2 groups; (1) CON, control animals and (2) NP-50 ($50{\mu}g/L$), animals were treated with NP via drinking water. NP exposures were continuously conducted from parental pre-mating period until the postnatal day (PND) 55 of F2 offsprings. Mice were sacrificed on PND 55 and the reproductive tissue weights were measured. The initial (at PND 21) and terminal (PND 55) body weights of the NP-50 group animals were not significantly different from those of control group animals. NP exposure fail to induce a significant weight change of the testes, seminal vesicle and prostate except absolute epididymal weight (p<0.05). However, pathohistological studies revealed that NP-treated F2 animals showed evident decrease in seminiferous tubule diameters, reduced luminal area and number of germ cells. Also, sloughing morphologies in the tubules were notable. In the caudal epididymis, fewer mature sperms and swollen epithelial cells were found in the NP-treated group. The present study demonstrated that the subchronic low-dose NP exposure induced pathohistological abnormalities in testis and epididymis of F2 mice, and we assumed that these 'qualitative' changes in reproductive tissues could be derived from the epigenetic modifications such as DNA methylation, histone modification, altered DNA accessibility and chromatin structure. Further studies are needed to achieve a better understanding on the multi- or trans-generational effects of NP on the reproductive health and a human application.

• Journal of Microbiology and Biotechnology
• /
• v.32 no.1
• /
• pp.46-55
• /
• 2022

Clostridioides difficile infection (CDI) is a significant cause of hospital-acquired and antibiotic-mediated intestinal diseases and is a growing global public health concern. Overuse of antibiotics and their effect on normal intestinal flora has increased the incidence and severity of infections. Thus, the development of new, effective, and safe treatment options is a high priority. Here, we report a new probiotic strain, Bacillus amyloliquefaciens (BA PMC-80), and its in vitro/in vivo anti-C. difficile effect as a prospective novel candidate for replacing conventional antibiotics. BA PMC-80 showed a significant anti-C. difficile effect in coculture assay, and its cell-free supernatant (CFS) also exhibited a considerable anti-C. difficile effect with an 89.06 ㎍/ml 50% minimal inhibitory concentration (MIC) in broth microdilution assay. The CFS was stable and equally functional under different pHs, heat, and proteinase treatments. It also exhibited a high sensitivity against current antibiotics and no toxicity in subchronic toxicity testing in hamsters. Finally, BA PMC-80 showed a moderate effect in a hamster CDI model with reduced infection severity and delayed death. However, further studies are required to optimize the treatment condition of the hamster CDI model for better efficacy and identify the antimicrobial compound produced by BA PMC-80.

• The Korea Journal of Herbology
• /
• v.28 no.1
• /
• pp.15-21
• /
• 2013

Objectives : To evaluate the safety of KOB, a polyherbal medicine for allergic rhinitis, we conducted a subchronic toxicology study. Methods : Dried extract of KOB(Lot. No. 11003, yield : 41.1%) was prepared from GLP company (Hanpoong Pharm & Food Co., Ltd). KOB was repeatedly administrated orally of male SD rats at daily dose levels of 500 (G2), 1250 (G3) and 5000 (G4) mg/kg/day for 13 weeks. We recorded the clinical signs of toxicity, body weight, food intake/consumption, optometry, urine analysis, organ weights, hematology, and conducted serum biochemical analysis, necropsy, gross and histological changes in target organs of Sprague-Dawley rats, and clinical chemistry analysis. Results : Neither death nor any toxicological signs were obserbed in KOB at all doses of 500, 1250 and 5000 mg/kg/day during the administration period for thirteen-week. Furthermore, there was no difference in body weight and food-take consumption, optometry, necropsy, organ weight, gross pathological findings, and urine analysis among the groups of rats treated with different doses of KOB, during at the observation period for thirteen-week. The hematological analysis and clinical blood chemistry data were revealed no toxic effects from repeated-dose administration of KOB in rats during the observation period. Conclusions : Based on these results, the no observable adverse effect level (NOAEL) of KOB was considered to be 5000 mg/kg/day for male rats under these study conditions.

• Journal of Sasang Constitutional Medicine
• /
• v.9 no.2
• /
• pp.203-225
• /
• 1997

Jihwangbakhotang(地黃白虎楊) is made by Li Je Ma, the creator of the Four Constitutional Medicine. Single and 13 weeks oral repeated dose toxicity studies were conducted in Sprague Dawley rats of both sexes to elucidate the potential acute and subchronic toxicity of JBT extract and reversibility of any effects. In the single dose study, JBT extract was administered orally to rats with the dose of 2 g/kg and 8 g/kg. In the long term administration of 13 weeks, the JBT extract of 125 mg/kg/day, 500 mg/kg/day, 2000 mg/kg/day was administered to rats. The change of blood weight, urine volume, electrolyte in urine, hematological change, the change of blood chemistry, autopsy finding, and histological observation were researched, the results were as follows; 1. The lethal dose of JBT extract seems to be over 10 g/kg, the single administration of JBT extract 8 g/kg showed no toxical signs except little increase of urine volume. 2. The change of body weight had the trend of decrease in the group of, but has no significance, and also the consumption of food and water had no changes. 3. The hematological changes induced by the 13 weeks administration of JBT extract showed the significance in the item of Hb, MCH, MCV, WBC in the group of 125 mg/kg/day. 4. In the test of blood chemistry, total cholesterol showed little decrease and A/G ratio showed little increase, but the change was not clear, and the standard error was large. So the result was obtained insignificantly and the toxicity of JBT extract was not observed. 5. In the male group after recovery period, the level of cholesterol and triglyceride decreased slightly, but the result was not significant. 6. In the urine test, the little change of electrolyte was appeared, but it seemed not to be the result induced by the toxicity of JBT extract. 7. In each group of male and female rats, the weight change of organ and the serum histological changes was observed, but the result did not showed the dose dependent toxicity. So the toxicity of JBT extract was not regarded. In the conclusion, the toxicity of JBT extract was not observed in the single dose treatment and long term repetitive administration of JBT extract.

• Biomolecules & Therapeutics
• /
• v.23 no.2
• /
• pp.156-164
• /
• 2015

Alzheimer's disease (AD) is a neurodegenerative disorder associated with progressive memory loss and neuronal cell death. Although numerous previous studies have been focused on disease progression or reverse pathological symptoms, therapeutic strategies for AD are limited. Alternatively, the identification of traditional herbal medicines or their active compounds has received much attention. The aims of the present study were to characterize the ameliorating effects of spinosin, a C-glucosylflavone isolated from Zizyphus jujuba var. spinosa, on memory impairment or the pathological changes induced through amyloid-${\beta}_{1-42}$ oligomer ($A{\beta}O$) in mice. Memory impairment was induced by intracerebroventricular injection of $A{\beta}O$ ($50{\mu}M$) and spinosin (5, 10, and 20 mg/kg) was administered for 7 days. In the behavioral tasks, the subchronic administration of spinosin (20 mg/kg, p.o.) significantly ameliorated $A{\beta}O$-induced cognitive impairment in the passive avoidance task or the Y-maze task. To identify the effects of spinosin on the pathological changes induced through $A{\beta}O$, immunohistochemistry and Western blot analyses were performed. Spinosin treatment also reduced the number of activated microglia and astrocytes observed after $A{\beta}O$ injection. In addition, spinosin rescued the $A{\beta}O$-induced decrease in choline acetyltransferase expression levels. These results suggest that spinosin ameliorated memory impairment induced through $A{\beta}O$, and these effects were regulated, in part, through neuroprotective activity via the anti-inflammatory effects of spinosin. Therefore, spinosin might be a useful agent against the amyloid ${\beta}$ protein-induced cognitive dysfunction observed in AD patients.