• Korean Journal of Food Science and Technology
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• v.8 no.1
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• pp.53-60
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• 1976

This study was undertaken to investigate the toxic effect of AF-2, 2-(2-furyl)-3-(5-nitro-2-furyl) acrylamide, in the diet of rats (Splague Dowley) for 4 weeks. Comparisons were made of weight gains, organ weights and the cholesterol, phospholipid and triglyceride content of the blood serum and liver tissue. Rats were divided into three groups, a control group which was fed on a standard diet and two groups were fed with 0.04% (group I) and 0.2% (group II) of AF-2. Male rats weighing 370-410 g, female rats weighing 240-250 g were used in this experiment and each group was composed of 24 Albino rats. The results were as follows. 1. Comparisons of weight gains, control and experimental groups did not show significant differences. 2. An examination of organ weights, liver weights of experimental groups showed higher than that of the control group. 3. In the lipid content of blood serum, phospholipid contents of experimental groups were lower than that of the control, while cholesterol and triglyceride content of experimental groups were higher than that of the control. 4. In the lipid content of liver tissue, phospholipid and triglyceride content of experimental groups did not show considerable changes, but cholesterol content was increased in proportion to AF-2 content. From these results, the authors could observe the significant changes in weight gains of liver and cholesterol content after feeding. It is concluded that the toxic effect of group II showed higher than that of group I and AF-2 had a toxic effect on rat liver to a certain extent.

• Radiation Oncology Journal
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• v.14 no.4
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• pp.281-290
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• 1996

Purpose : Chest irradiation leads to a significant cardiac injury in a number of patients. To prevent, or to reduce the risk of radiation-induced cardiac injury, pentoxifylline(PTX), a haemorrheologic agent that improves the blood flow through small blood capillaries has been employed. Materials and Methods : One hundred and eighty ICR mice were divided into three study groups: control, radiation alone, and radiation-pentoxifylline. Each group was subdivided into 12 subgroups: 1 3, 6 and 10 days and 2, 3, 4, 6, 8, 12, 16 and 20 weeks by observation Period after irradiation. The total 15Gy of radiation was delivered in a single fraction through anterior mediastinal port. Pentoxifylline was injected subcutaneously daily 50mg/kg to the back of the mice from the first day of irradiation throughout the observation period. The mice of each group after a certain observation period were sacrificed and sectioned for histopathologic examination of the heart. Result : The findings of acute radiation-induced carditis i.e., heterophilic infiltration and vacuolization and ballooning of endothelial cells were observed upto 6 weeks and reduced sharply afterwards. The late radiation effects including pericarditis with mononuclear cell infiltration, pericardial fibrosis, endothelial cell changes, myocardial degeneration and fibrosis present from 4 weeks onwards after irradiation but with various degree of severity. The overall process of pathologic changes of radiation-pentoxifylline group was similar to those of radiation alone group but the duration of acute stage was relatively short and the severity of late cardiac toxicity was much lesser compared with those of radiation alone group. Conclusion : Pentoxifylline can effectively reduce the late radiation-induced cardiac injury and reslve the acute effects relatively rapidly.

• Food Engineering Progress
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• v.21 no.4
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• pp.318-325
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• 2017

Alcoholic steatosis is a fundamental metabolic disorder and may precede the onset of more severe forms of alcoholic liver disease. In this study, we isolated enzymatichydrolysate from Semisulcospira libertine by alcalase hydrolysis and investigated the protective effect of Semisulcospira libertine hydrolysate on liver injury induced by alcohol in the mouse model of chronic and binge ethanol feeding (NIAAA). In an in vitro study, the hydrolysate protects HepG2 cells from ethanol toxicity. Liver damage was assessed by histopathological examination, as well as by quantitating activities of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP). After the administration of S. libertina hydrolysate, fat accumulation and infiltration of inflammatory cells in liver tissues were significantly decreased in the NIAAA mouse model. The elevated levels of serum AST, ALT, and ALP activities, along with the lipid contents of a damaged liver, were recovered in experimental mice administrated with S. libertina hydrolysate, suggesting its role in blood enzyme activation and lipid content restoration within damaged liver tissues. Moreover, treatment with S. libertine hydrolysate reduced the expression rate of cyclooxygenase (COX-2), interleukin $(IL)-1{\beta}$, and IL-6, which accelerate inflammation and induces tissue damage. All data showed that S. libertine hydrolysate has a preventive role against alcohol-induced liver damages by improving the activities of blood enzymes and modulating the expression of inflammation factor, suggesting S. libertine hydrolysate could be a commercially potential material for the restoration of hepatotoxicity.

• Herbal Formula Science
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• v.15 no.1
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• pp.185-197
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• 2007

Objective : This study was conducted to investigate the effects of Hwangryunhaedok-Tang and Geongangbuja-Tang on the change of interleukin-6 (IL-6) and tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$) level induced by LPS I.C.V. injection in mice. Method : We devided group into 6 mice and 6 mice were assingned to each group. In the normal group only saline was administered intragastrically, and in the control group LPS was injected intracerebroventricularly 1 hr after intragastric administration of saline. In the experiment groups Hwangryunhaedok-Tang(0.5g/kg, 1.0g/kg, 3.0g/kg) was administered intragastrically to mice 1 hr prior to LPS(100mg/mouse) I.C.V. injection.. Also Geongangbuja-Tang (0.5g/kg, 1.0g/kg, 3.0g/kg) was administered intragastrically to mice 1 hr prior to LPS(100mg/mouse) I.C.V. injection. To measure the plasma IL-6 and $TNF-{\alpha}$ level of mice, their blood samples were collected from retro-orbital plexus, immediately centrifuged at $4^{\circ}C$, and plasma was removed and stored frozen at $-83^{\circ}C$ for later determination of IL-6 and $TNF-{\alpha}$. The level of IL-6 and $TNF-{\alpha}$ production was measured by enzyme-linked immunosorbent assay in the plasma. Result : Regarding IL-6 level, The 0.5g/kg and the 1g/kg groups of Geongangbuja-Tang decreased IL-6 level. Especially the 3g/kg control group decreased IL-6 level significantly than the normal group(p<0.01). Regarding $TNF-{\alpha}$ level, the 3g/kg group of Geongangbuja-Tang decreased it significantly(p<0.05). Conclusion : These data revealed that Hwangryunhaedok-Tang might not have the anti imflammatory effect and Geongangbuja-Tang(3g/kg)might have the anti imflammatory effect by reducing the plasma IL-6 and $TNF-{\alpha}$ level in mice LPS Injection.EIM (Eighteen Incompatible Medicaments) is an important component in Oriental pharmacology and is directly related to clinical prescriptions. Medical practitioners argued that the definite cause and meaning of EIM was ambiguous and therefore debated the issue of clinical application of the EIM. This study conducted an in-depth literary research on the origin, meaning and contents of EIM with the purpose to contribute in its efforts to be used clinically. Even after thousands of years have past since establishment of Oriental medicine, EIM is still tabooed and was an obstacle that hindered ideologies. Modern herbal medicine texts claim that the use of EIM can reduce treatment effects and promote poisoning and side effects. However, since long ago, there has been medical practitioners who reject this as false. Recently, poisoning caused by EIM has been claimed to be from the toxicity of the drug itself, rather than the result of interaction between the drugs, and therefore they suggest that EIM is not a forbidden domain. In addition, EIM showed a difference in number depending on the era. However, this can be understood not as a definite number, but instead as a warning to be careful during combination of drugs for use as clinical medicine. Historically, there were very few cases in which EIM was used for clinical tests and thus, the clinical value is not, while others applied EIM directly to their bodies, which showed signs for the usefulness and potential of EIM for us. A more concrete and in-depth study must be made on EIM.

• Journal of Life Science
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• v.23 no.6
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• pp.812-824
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• 2013

Reserpine, an anti-hypertensive drug, is able to positively modulate several phenotypes associated with $A{\beta}$ toxicity in a Caenorhabditis elegans model of Alzheimer's disease (AD). We investigated into the therapeutic effects of reserpine on mammalian neurodegenerative disorders, and found that significant alteration of the key factors influencing AD was detected in Tg2576 mice after reserpine treatment for 30 days. The aggressive behavior of Tg2576 mice was significantly improved upon reserpine treatment, whereas their social contact was consistently maintained. Furthermore, the levels of $A{\beta}$-42 peptide in the hippocampus of the brain and blood serum were lower in the reserpine-treated group than in the vehicle-treated group. Among g-secretase components, the expression levels of PS-2, Pen-2, and APH-1 were slightly lower in reserpine-treated Tg2576 mice, although a significant change in nicastrin (NCT) expression was not detected. Furthermore, the serum level of nerve growth factor (NGF) increased in reserpine-treated Tg2576 mice compared with vehicle-treated mice. Among down-stream effectors of the NGF receptor TrkA signaling pathway, reserpine treatment induced elevation of TrkA phosphorylation and reduction of ERK phosphorylation. In addition, in the NGF receptor $p75^{NTR}$ signaling pathway, the expression levels of $p75^{NTR}$ and Bcl-2 were enhanced in reserpine-treated Tg2576 mice compared with vehicle-treated mice, whereas the expression level of RhoA declined. Overall, these results suggest that reserpine can help relieve AD pathogenesis in Tg2576 mice through downregulation of $A{\beta}$-42 deposition, alteration of ${\gamma}$-secretase components, and regulation of NGF metabolism.

• Journal of Chest Surgery
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• v.32 no.7
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• pp.613-620
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• 1999

Background: Recently, regional or isolated organ perfusion is being studied again as a drug administration modality which is able to reduce systemic toxicity while delivering high-dose chemotherapeutic agents. This research was planned to evaluate the pharmacokinetics and long-term pathologic changes of the lung in isolated lung perfusion (ILP) with cisplatin. Material and Method: Twenty-five New Zealand white rabbits were divided into 2 groups (Group I: 10, Group II: 15). The groups were then subdivided into 2 and 3 subgroups of 5 rabbits. In group I, tissue samples of the lung and kidney, and systemic blood for platinum concentration measurement were taken 30 minutes after systemic intravenous infusion of cisplatin (5 mg/kg) and isolated lung perfusion in each 5 rabbits. In 2 subgroups of group II, lung tissues for pathologic exams were taken 30 minutes and 1 week after ILP in each 5 rabbits, which received 10% pentastarch solution only and cisplatin, respectively. In the other subgroups, lung biopsy was undertaken 4 weeks after ILP with cisplatin. Result: When cisplatin was infused via systemic vein, the platinum concentration in the lung, kidney and plasma were 1.50${\pm}$0.43 $\mu\textrm{g}$/g, 7.65${\pm}$2.49 $\mu\textrm{g}$/g, 1.19${\pm}$0.03 $\mu\textrm{g}$/ml, respectively. However, the platinum concentration in the lung was about 50 times higher (75.43${\pm}$11.47 $\mu\textrm{g}$/g) than that of intravenous infusion group, and those in the kidney and plasma were decreased (1.30${\pm}$ 0.35 $\mu\textrm{g}$/g, 0.13${\pm}$0.02 $\mu\textrm{g}$/ml) when cisplatin was introduced through ILP. Pathologic change in the treated lung with ILP was characterized by the medial hypertrophy of the pulmonary arterioles and interstitial eosinophilic infiltration, which was not dependent on cisplatin

• Korean Journal of Food Science and Technology
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• v.49 no.6
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• pp.676-684
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• 2017

The present study aimed to examine the hepatoprotective effects of ethanol extracts from steam-dried ginseng berry (SGBE) in both $\text\tiny{D}$-Galactosamine/Lipopolysaccharide ($\text\tiny{D}$-GalN/LPS)-sensitized mice and in vitro models. Our results clearly demonstrated that SGBE significantly reduced the level of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and lactate dehydrogenase in blood, and $TNF{\alpha}$ was normalized in 8 h after the treatment with $\text\tiny{D}$-GalN/LPS. Coincidently, major organs remained unimpaired when compared to $\text\tiny{D}$-GalN/LPS control group. Moreover, p38, which stimulates expression of NAFLD-associated cytokines, was markedly inhibited when treated with SGBE. In vitro analysis revealed that the main components of SGBE, linoleic acid and ginsenoside Re/Rd, may play a role in protecting liver from $\text\tiny{D}$-GalN/LPS-induced toxicity. Finally, we concluded that SGBE may be a promising therapeutic agent for preventing damage to the liver.

• Journal of Preventive Medicine and Public Health
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• v.31 no.2 s.61
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• pp.275-284
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• 1998

Activities of enzymes involved in the metabolism of various carcinogenic xenobiotics is one of the most important host factors for cancer occurrence. N-acetyltransferase (NAT) and glutathione S-transferases (GST) are enzymes which .educe the toxicity of activated carcinogenic metabolites. Slow N-acetylation and lack of GST mu (GSTMI) were reported as risk factors of bladder cancer. GST theta (GSTT1), which is another type of GST, was reported to be deleted at higher proportion among Koreans. Since cause of bladder cancer is not fully explained by single risk factor, many kinds of enzymes would be involved in the metabolism of carcinogens excreted in urine. This study was performed to investigate whether the polymorphisms of NAT2, GSTM1 and GSTT1 are risk factors of bladder cancer and to evaluate the effects of their interaction on bladder cancer development. Sixty-seven bladder cancer and 67 age- and sex-matched non-cancer patients hospitalized in Chungbuk National University Hospital from March to December 1996, are the subjects of this case-control study. Questionnaire interview was done and the genotypes of NAT2, GSTM1 and GSTT1 were identified using PCR methods with DNA extracted from venous blood. The effects of the polymorphism of NAT2 and GSTM1 and their interaction on bladder cancer were statistically tested after controlling the other risk factors. The frequencies of slow, intermediate, and rapid acetylators were 3.0%, 38.8%, and 58.2% to. the cases, and 7.6%, 40.9%, and 51.5% for the controls, respectively. The risk of bladder cancer was not associated with the increase of NAT2 activity($\chi^2_{trend}=1.18$, P-value>0.05). GSTM1 was deleted in 68.7% of the cases and 49.3% of the controls ($\chi^2=5.21$, P-value<0.05), and the odds ratio (95% CI) was 2.23 (1.12 - 4.56). GSTT1 deletion, the .ate of which were 26.9% for the bladder cancer patients and 43.3% for the controls, was a significant protective factor against bladder cancer. Smoking history turned out to be insignificant as a risk factor of bladder cancer (OR=1.85, 95% CI: 0.85 - 4.03), and occupation could not be tested because of the extremely small number of occupational history related to the increase of bladder cancer. In multiple logistic analysis controlling the effects of other risk factors, GSTM1 deletion was the only significant risk factor for bladder cancer (OR: 2.56, 95% CI: 1.22-5.36, P-value<0.05), but slow acetylation and GSTT1 deletion were not. These results suggest that GSTM1 deletion may be a significant risk factor of bladder cancer. Since there have been much debates on causal relationship between slow acetylation and GSTT1 deletion, and bladder cancer, further studies are needed.

• Korean Journal of Ecology and Environment
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• v.36 no.1 s.102
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• pp.83-94
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• 2003

Concentrated releases of zinc into water usually results from discharges associated with industrial purpose. The released zinc into soil is corroded and released into water. In aquatic environment, exess zinc is toxic to the organisms and causes the growth inhibition and malformation of them as a heavy metal. In this study, excess zinc toxicity was tested by FETAX (frog embryo teratogenetic assay with Xenopus)as in vivo system. Xenopus embryos at st.9 were exposed to $100{\sim}900\;{\mu}M$ of zinc for 7 days and 81% of individuals were survived in 100 ${\mu}M$, and 25% were survived in 1000M of zinc solution. In external malformations, swelled belly and intestinal dysplasia were common, and all of tested individuals showed these malformations in 200 ${\mu}M$ or higher concentration of zinc. In 400 ${\mu}M$ or higher concentration, all of tested tadpoles showed faded heart. Also, hypo-pigmentation, lens hernia and loose digestive track were very frequently found in 100 ${\mu}M$ of zinc. The histological study with paraffin section of zinc treated tadpoles showed following abnormalities; regeneration of photoreceptor on retina, reduced vitreous chamber in eye, reduction of red blood cells in heart, abnormal liver, swelling of pronephric cell, muscle dysplasia and palatal papilloma. These abnormalities may be caused by the degeneration of mitochondria, inhibition of cell adhesion, and the formation of leghemoglobin by zinc due to the substitution of $Ca^{2+}$ by $Zn^{2+}$. The body length was reduced due to the excess zinc. From a statistical result, body lengths of 300 ${\mu}M$ or higher concentrative g개ups was significantly reduced comparing that of control group. Recently, many spontaneous malformations and reduction of amphibians are reported, From the results of present study, excess zinc mi호t be a factor of amphibian reduction, and the control of zinc discharges is very important.

• Pediatric Infection and Vaccine
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• v.12 no.1
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• pp.75-85
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• 2005

Purpose : Fungal infection is one of the important causes of morbidity and mortality in patients with hematologic malignancies. Amphotericin B(ABV) and itraconazole(ITZA) have been used as the standard empirical antifungal therapy in neutropenic patients with acute leukemia who have persistent fever that does not respond to antibiotic therapy. ABV is an antifungal drug associated with side effects such as fever and chills, symptoms which may be mediated by pro-inflammatory cytokines such as interleukin-$1{\beta}$(IL-$1{\beta}$) and tumor necrosis factor-${\alpha}$(TNF-${\alpha}$). We assessed modulation of these pro-inflammatory cytokines as well as the anti-inflammatory cytokines(IL-4, IL-1Ra) by ABV and ITZA. Methods : From March 2004 to February 2005, a total of 30 episodes from acute leukemia patients with febrile neutropenia were analyzed for this study. They were randomly allocated to receive intravenous ABV or ITZA for 14 days. Clinical responses were evaluated at the completion of therapy, and cytokine IL-$1{\beta}$, TNF-${\alpha}$, IL-4, and IL-1Ra were measured for determination to know the correlation between two antifungal agents and inflammatory cytokines. Results : Empirical antifungal agents were given to 37 patients(ABV 20, ITZA 17), and 30 patients(ABV 15, ITZA 15) were evaluable for efficacy. White blood cell and absolute neutrophil count in the group treated with ITZA increased early days of treatment, so the duration of neutropenia in ITZA group is shorter. Serum creatinine level is lower in ITZA group than in ABV group but this is not statistically significant. There was no significant difference in response rate between two groups. The IL-$1{\beta}$ was increased in ABV treatment group and the ratio of IL-1Ra/IL-$1{\beta}$ is markedly decreased in ABV treatment group while increased in ITZA group. Conclusion : ITZA and ABV have at least equivalent efficacy as empirical antifungal therapy in neutropenic children with acute leukemia. However ITZA is associated with significantly less toxicity in clinical and molecular aspects.