• Toxicological Research
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• v.34 no.1
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• pp.41-48
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• 2018

The efficacy of highly active antiretroviral therapy (HAART) has led to an increase demand for therapeutic use, thereby necessitating investigation into drug toxicity. This study was designed to investigate the in vivo effects of HAART on sperm parameters and testicular oxidative stress in lean and obese rats. Wistar rats (males, n = 40, weighing 180~200 g) were assigned randomly into 4 groups and treated accordingly for 16 weeks as follows: Control (C): lean group fed with standard rat chow; Diet induced obesity (DIO): obese animals fed a high caloric diet; C + ART: lean animals treated with HAART; DIO + ART: obese animals treated with HAART. An antiretroviral drug combination of Tenofovir, Emtricitabine and Efavirenz at a dose of 17, 26 and 50 mg/kg/day was administered for the latter 6 weeks via jelly cube feeding. At the end of the experimental period, sperm analysis was performed on sperm collected from the caudal epididymis, while the testis was homogenized for antioxidant enzyme and lipid peroxidation assays. Results showed that HAART significantly decreased sperm motility (p < 0.05) in both lean and obese animals, and viability (p < 0.05) in the DIO group. Testicular glutathione, catalase and superoxide dismutase were significantly decreased (p < 0.05), while Thiobarbituric acid reactive substances (TBARS) levels were significantly increased (p < 0.05) when the DIO+ART group was compared to Control group. Thus, the decreased sperm qualities associated with HAART might be as a result of increased testicular oxidative stress prominent in obese animals.

• The Journal of Internal Korean Medicine
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• v.30 no.3
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• pp.481-494
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• 2009

Background : Radix Sophora Flavescentis (SF) is used for the treatment of diabetes mellitus in Traditional Korean Medicine. However, little is known about the effects of Radix Sophora Flavescentis extract (SFE) on the hypoglycemic mechanism. Objective : We performed a series of experiments to verify the effects of SFE on the proliferation of RIN-m5F, the secretion and synthetic processes of insulin with glucose stimulation and inhibition of $\alpha$-glucosidase. Methods : Various amounts of SFE were added to the RIN-m5F cell culture to identify the effects on the cell proliferation, total amounts of insulin secretion, and related gene expression at the molecular level. Also to identify the inhibitory effect on the $\alpha$-glucosidase activities, ${\rho}NPG$ assay was done with various SFE concentrations followed by comparison with control. Results : SFE did not show considerable effects on RIN-m5F cells proliferation, insulin secretion or insulin mRNA expression, whichever phenomena did not depend on the glucose concentration. However, SFE significantly inhibited $\alpha$-glucosidase activity in a dose dependent manner compared to control. Conclusions : This study showed that SFE has potent $\alpha$-glucosidase inhibitory activity. Thus, SF may by used for the improvement of overall glycemic control. Further mechanism studies on the lipid toxicity and oxidation stress of SF seem to be necessary.

• Journal of Physiology & Pathology in Korean Medicine
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• v.16 no.2
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• pp.296-302
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• 2002

Bohyulmyunyuk-dan is an Oriental herbal formulation to enhance the general body conditions as well as immune response against both endogenous and exogenous harmful challenges. This study was designed to investigate the effect of Bohyulmyunyuk-dan on the cisplatin-induced toxicity of primary rat astrocytes and C6 glioma cells. After trestment of astrocytes and C6 glioma cells with cisplatin, MTT assay was carried out to measure cytotoxicity of brain cells. To explore the mechanism of cytotoxicity, astrocytes were treated with Bohyulmyunyuk-dan and followed by the addition of cisplatin. Then, the protective effects of Bohyulmyunyuk-dan were investigated in apoptosis signaling pathway. The results were obtained as follows ; Bohyulmyunyuk-dan protected the death of astrocytes by cisplatin, which decreased the viability of astrocytes and C6 glioma cells in a time- and dose-dependent manner. Bohyulmyunyuk-dan protected the apoptotic death of astrocytes from cisplatin induced cell apoptosis. Bohyulmyunyuk-dan inhitited the activation of caspase-3 and -9 protease in astrocytes by cisplatin. Bohyulmyunyuk-dan inhibited the deavage of PARP in astrocytes by cisplatin. According to above results, Bohyulmyunyuk-dan may prevent brain cells from cytotoxicity induced cell apoptosis induced by chemotherapeatic agents induding displatin.

• Journal of Veterinary Clinics
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• v.27 no.2
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• pp.163-169
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• 2010

To evaluate of oral toxicity of Epimedium koreanum nakai (EKN) water extract, three doses of EKN water extract (10, 100 and 1000 mg/kg/day) were administered to healthy Sprague-Dawley rats for 4 weeks. The results showed that there are no abnormal signs during the experimental period. The weights of testis and epididymis were increased dose-dependently, but seminal vesicle was decreased compared with control group. In hematology and serum chemistry, changes were observed within the normal ranges. In histological finding, slight to moderated changes were found but those were commonly or rarely encountered in the normal rats. These results suggest that no observed adverse effect level (NOAEL) of the oral application of EKN was considered to be more than 1000 mg/kg in SD rats under the conditions employed in this study.

• Korean Journal of Pharmacognosy
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• v.40 no.4
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• pp.400-407
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• 2009

The purpose of this study is to investigate hypotensive effect of BDR-29, new herbal preparation of Cassiae Semen, Prunellae Spica, Uncariae Ramulus et Uncus, and Tribuli Semen, in stroke-prone spontaneously hypertensive rats (SHR-SP). SHR-SP were treated with BDR-29 at a dose of 100, 200 mg/kg/day orally for 13 weeks. In the BDR-29 treat group, mean blood pressure and systolic blood pressure were significantly reduced (p<0.05). In phenylephrine-precontracted arota and carotid artery, BDR-29 induced endothelium-dependent vascular relaxation. Hematological findings and biochemical examination revealed no evidence of specific toxicity related to BDR-29. In addition, BDR-29 was markedly attenuated intima-media thickness of thoracic aorta with progression of atherosclerosis. SHR-SP were treated with BDR-29 were significantly increased eNOS expression in arota. These results indicated that BDR-29 improves blood pressure as well as initial atherosclerotic lesion.

• Journal of Society of Preventive Korean Medicine
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• v.12 no.1
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• pp.89-102
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• 2008

Purpose : The experiments was undertaken to evaluate the effects of herbal medicine, Ojeoksan, in pregnant rats Methods : Female Sprague-Dawley rats were orally administered with the Ojeoksan at dose of 5mg/kg/day for 20 days. Pregnant rats were sacrificed at 20th day of gestation, and observed internal and reproductive organs. Approximately live fetuses in the 20th day of gestation were randomly selected and fixed in 95% ethanol. Results : Maternal body weight of Ojeoksan treated group has a tendency to increase compared to that of control group. There were no significant difference in internal and reproductive organs. There were no significant changes between two groups in blood chemistry and hematological values. There were no significant changes in number of corpus luteum, implantation, live fetuses and sex ratio. But Ojeoksan administered group showed higher delivery rate, early resorption rate than the control group. Also Ojeoksan administered group showed higher implantation rate, late resorption rate than the control group. Conclusion : From these results, it can be concluded that Ojeoksan showed no toxicity effects on maternal body weight and number of live fetuses. There were no significant changes in organ weight, hematological data, reproductive organs. We need more precise study to investigate the mechanism of early or late resoption by the herbal medicines such as Ojeoksan.

• Toxicological Research
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• v.17
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• pp.281-287
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• 2001

The Artichoke extract at 10% was used to add in drinking water to understand its effect on Aflatoxicosis of chickens. The Artichoke extract at the dose of 6 ml per liter of drinking water was given (experiment group) or not (control group) and to Hybro chickens (150 birds), during the first 49 days of life. Also, the chickens were fed with foodstuff containing 200 ppb or 500 ppb Aflatoxin $B_1$. Results showed that, the chickens having Artichoke extract: (1) Had overcome the growth retardation caused by the toxin at concentration of 200 ppb and 500 ppb of Aflatoxin $B_1$ (an addittonal weight gain of about 200-400 g/bird). (2) The feed conversion was improved (a reduction of 200-400 g of feed per kg of bird living weight). (3) Aflatoxicosis lesions were mild in the chickens, which fed 500 ppb of Aflatoxin $B_1$ or not found in those having the toxin 200 ppb. The blood examinations at 28th and 49th days of the trial gave the following results: (1) The Artichoke extract had an effect of suppressing the changes of blood cell numbers, hemoglobin amount. packed cell volume. leukocyte formula that were caused by Aflatoxin $B_1$. (2) The Artichoke extract had an effect of suppressing the diminution oj sugar, protein levels and the increase of the levels of GOT, GPT, alkaline phosphatase and bilirubin in the blood of intoxicated chickens. There was not or very Jew residue of Aflatoxin $B_1$ contained in the liver and muscle of chickens intoxicated by Aflatoxin $B_1$ having Artichoke, that was much lower than the allowed level in animal products.

• Toxicological Research
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• v.16 no.4
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• pp.317-323
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• 2000

The immunosuppressive effects of thirty nine chemicals chosen by their potential toxicity were evaluated using a three-step testing method. The immunotoxicity test method developed in this study consisted of three simple assays of lymphoproliferation, mixed leukocyte response, and interleukin (IL)-2 production. The first step was mitogen-induced proliferation assay. Ten chemicals showed the inhibitory effects on the mitogen (lipopolysaccharide or concanavalin A)-induced proliferation in dose-dependent manners. The second step was mixed lymphocyte response. This step crosschecked the growth-suppressive effects detected at the first step. All of 10 chemicals, which showed suppression of lymphoproliferation, also exhibited the suppressive effects on the mixed lymphocyte response in the similar range of chemical concentration. The third step was planned to determine whether or not this growth suppression was mediated through an early activation of T-cell, which could be represented with IL-2 production. Six out of 10 chemicals decreased the interleukin-2 production in the similar concentration range used in the step 1 and 2. These results suggest that those 6 chemicals might have their targets on the signal transduction path-way toward the IL-2 production. In the meantime the other 4 chemicals might have their targets after the IL-2 production signal. Taken all together, the three-step test would be simple, fast, and efficient to deter-mine whether or not the chemical has immunosuppressive effects.

• Radiation Oncology Journal
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• v.30 no.4
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• pp.165-172
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• 2012

Purpose: To retrospectively evaluate the outcome and toxicity of total lymphoid irradiation (TLI) based conditioning regimen for allogeneic hematopoietic stem cell transplantation (HSCT) in severe aplastic anemia (SAA) patients who experienced an engraftment failure from prior HSCT or were heavily transfused. Materials and Methods: Between 1995 and 2006, 20 SAA patients received TLI for conditioning of HSCT. All patients were multi-transfused or had long duration of disease. Fifteen (75%) patients had graft failure from prior HSCT. In 18 (90%) patients, the donors were human leukocyte antigen identical siblings. The stem cell source was the peripheral blood stem cell in 15 (75%) patients. The conditioning regimen was composed of antithymocyte globulin plus TLI with a median dose of 750 cGy in 1 fraction. The graft-versus-host disease (GVHD) prophylaxis used cyclosporine with methotrexate. Results: With a median follow-up of 10.8 years, graft failures developed in 6 patients. Among them, 3 patients received their third HSCT to be engrafted finally. The Kaplan-Meier overall survival rate was 85.0% and 83.1% at 5 and 10 years, respectively. The incidence of acute and chronic GVHD was 20% and 20%, respectively. None of the patients have developed a malignancy after HSCT. Conclusion: In our study, TLI based conditioning in allogeneic HSCT was feasible with acceptable rates of GVHD in SAA patients who experienced graft failure from prior HSCT or was at a high risk of graft rejection. We achieved relatively better results of engraftment and survival with a long term follow-up.

• Radiation Oncology Journal
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• v.31 no.4
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• pp.216-221
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• 2013

Purpose: The purpose of this retrospective study was to evaluate the efficacy and feasibility of short-course hypofractionated radiotherapy (RT) for the palliation of uterine cervical cancer. Materials and Methods: Seventeen patients with cancer of the uterine cervix, who underwent palliative hypofractionated 3-dimensional conformal radiotherapy between January 2002 and June 2012, were retrospectively analyzed. RT was delivered to symptomatic lesions (both the primary mass and/or metastatic regional lymph nodes). The total dose was 20 to 25 Gy (median, 25 Gy) in 5 Gy daily fractions. Results: The median follow-up duration was 12.2 months (range, 4 to 24 months). The median survival time was 7.8 months (range, 4 to 24 months). Vaginal bleeding was the most common presenting symptom followed by pelvic pain (9 patients). The overall response rates were 93.8% and 66.7% for vaginal bleeding control and pelvic pain, respectively. Nine patients did not have any acute side effects and 7 patients showed minor gastrointestinal toxicity. Only 1 patient had grade 3 diarrhea 1 week after completion of treatment, which was successfully treated conservatively. Late complications occurred in 4 patients; however, none of these were of grade 3 or higher severity. Conclusion: Short-course hypofractionated RT was effective and well tolerated as palliative treatment for uterine cervical cancer.