• 대한수의학회지
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• 제40권2호
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• pp.361-371
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• 2000

최근 2-bromopropane(2-BP)이 사람과 실험동물에서 정소독성을 유발한다고 보고된 바 있다. 그러나 수컷 생식기계에 있어서 2-BP의 지연효과에 대해서는 세부적으로 조사된 바가 없다. 본 연구는 Sprague-Dawley 랫드에서 2-BP의 정소독성과 정자발생의 회복을 조사하기 위하여 수행하였다. 5주령의 수컷 랫드에게 2-BP를 1,000mg/kg 용량으로 4주간 반복투여하였고, 투여시작후 1, 2, 3, 4 및 12주째에 부검하였다. 정소독성의 평가는 병리조직학적인 질적평가와 생식기관 중량, 정자두부수 및 재생지수 등의 양적평가로 수행하였다. 시험결과 2-BP를 투여한 랫드에서는 체중과 정소 및 정소상체 중량이 대조군에 비해 시간의존적인 방식으로 억제 또는 감소하였다. 병리조직검사에서는 투여 1주째에 stage I~IV에서 정조세포와 stage VII~IX에서 세사전기 및 세사기의 정모세포가 현저하게 소실되었다. 정조세포는 투여 2주째에 모든 stage에서 광범위하게 소실되었으며, 정자발생주기가 진행됨에 따라 2, 3 및 4주째에는 접합기 정모세포, 비후기 정모세포 및 원형 정자세포가 전구세포의 결손에 의해 점진적으로 소실되었다. 지지세포의 기능적 이상을 암시하는 지지세포의 공포화와 정자세포 저류는 상기한 모든 시기에서 관찰되었다. 8주 회복후인 12주째에는 대부분의 곡세정관이 심하게 위축되어 지지세포만 관찰되었으며, 간질조직에서는 간질세포의 과형성이 인정되었다. 또한 2-BP에 의해 유발된 정소의 손상이 비가역적임을 암시해주는 정자두부와 재생지수의 현저한 감소가 관찰되었다. 상기결과는 랫드의 2-BP를 1,000mg/kg의 용량으로 4주간 반복투여하면 정조세포의 결손에 의해 점진적으로 생식세포가 감소하고 이로 인하여 장기적인 정소위축이 유발된다는 것을 암시해준다.

• 한국환경보건학회지
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• 제20권2호
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• pp.64-72
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• 1994

Tolerance to toxic effects of cadmium (Cd), including lethality has been shown following pretreatment with cadmium and zinc. This study was designed to determine if tolerance also develops to Cd-induced hepatotoxicity and renal toxicity. Three groups of rats (A, B, C), each consisting of 108 rats, were studied and each group was divided into three subgroups (1, 2, 3), 12 rats for each subgroup. Rats were subcutaneously pretreated with saline (A), CdCl$_2$ (0.5 mg/kg, B), and ZnCl$_2$ (13.0 mg/kg, C) during time periods of 5 days. At the end of the period, rats were challenged with CdCIa (3.0 and 6.0 mg/kg) by intraperitoneal injection. As for the cadmium levels in rat tissues after pretreatments, it was highest in the liver. Then kidney, heart, blood and muscle followed it in that order. After 24, 48 and 96 hours of intraperitoneal injection by challenge doses the concentration of cadmium in liver and kidney increased proportionally to the increase of challenge dosage. However metallothioneins in liver and kidney were increased by the pretreatment of cadmium and zinc. These data indicate the liver is a major target organ of acute Cd poisoning, and suggest that cadmium induced hepatic injury, via release of Cd-MT, may play and important role in the nephrotoxicity observed in response to short-term exposure to cadmium. This result suggests that increasing cadmium concentrations, gradually accumulating in liver and kidney as the result of the pretteatmerit, served to induced the synthesis of metallothionein, thus making them resistant to the challenge from cadmium.

• 대한약침학회지
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• 제8권1호
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• pp.21-30
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• 2005

Objectives : To observe physiological anti-body effects of anti-BV, acute toxic response, measurement of $LD_{50}$, and the effects of anti-body were evaluated. Methods : $LD_{50}$ of Anti-Bee Venom were measured, and to analyze acute toxic responses, weight, and the anti-body effects various concentrations of Anti-BV were diluted and the survival rate was measured. Cell blood count (CBC), liver, spleen, and kidney pathologies were observed from the histological aspects. Results : Experiment was conducted to observe Anti-BV as the anti-body to the bee venom and the following results were obtained : 1.anti-BV was injected intraperitoneally and no toxic responses were witnessed. All of the experiment subjects stayed alive during the experiment, making $LD_{50}$ analysis impossible. 2.Anti-BV was injected intraperitoneally in mice and no significant weight changes were measured between the control group and the experiment groups. 3. Measuring the concentration dependent survival rate, the highest survival rate was at the concentration of $1.25{\times}10^2mg/kg$(1/2.000) for Anti-BV. 4. No particular results were shown in the CBC test. 5. Observation of changes in the organ tissues, Anti-BV was found to suppress blood stasis in the liver and inhibit necrosis of the cells. Conclusion : Above results suggest that Anti-BV doesn't cause any toxic responses in the body and works as an anti-body to the bee venom. Further studies must be followed to secure the findings.

• Toxicological Research
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• 제21권1호
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• pp.23-29
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• 2005

A developmental study of CONP01, a new antiarthritic agent, was conducted in Sprague-Dawley rats. Dosage of CONP01 0, 111, 333, and 1000 mg/kg/day were administered to dams orally from day 6 to day 16 of gestation. Two-third of dams per group were subjected to caesarean section on day day 20 of pregnancy for examination of their fetuses, and the remaining one-third of dams per group were allowed to deliver naturally for postnatal examination of their offspring. There was no change in the dams body weights, food consumptions, specific clinical sings and gross findings. There was significant decrease only in the absolute and relative weights of right ovary in 111 mg/kg treatment group, when compared with the vehicle control, whereas other organ weights were not changed. Moreover, no increase in the frequencies of external, visceral and skeletal malformation of fetuses were observed in the treated groups. These results suggest that the oral NOAEL (no observed adverse effect level) of CONP01 may be over 1,000 mg/kg in dams and fetuses of rats.

• Journal of Pharmaceutical Investigation
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• 제33권4호
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• pp.287-292
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• 2003

A novel antitumor agent, antibody-endostatin fusion protein $(anti-HER2/neu\;IgG3C_H3-Endostatin,\;AEFP)$ formed by genetic engineering procedure from antibody (Ab) which specifically targets to tumor cells ad angiogenesis inhibitor, endostatin (Endo) that has excellent antitumor effect, minimizes the toxicity of normal cells and selectively kills only tumor cells. The purpose of this study is to evaluate the phamacokinetic parameters and to analyze the localization of AEFP. After an intravenous injection of $150\;{\mu}l\;(5\;{\mu}Ci)\;[^{125}I]Ab,\;[^{125}I]AEFP$ to mice, blood was collected though retroorbital plexus from 15 min to 2880 min. Following the jugular vein injetion of $150\;{\mu}l\;(10\;{\mu}Ci)\;[^{125}I]Endo$, blood was collected by the use of carotid artery cannulation from 0.25 min to 30 min. Consequently, Endo was very rapidly removed from plasma compartment within 30 min. On the other hand, AEFP similar to Ab was slowly cleared from plasma. Also, Endo was metabolized about 40% within 30 min. However, AEFP was shown to metabolize less than 10% within 2880 min. The organ distribution of Endo was in order kidney, lung, spleen. Both Ab and AEFP were localized in order spleen, kidney, liver. Futhermore the tumor/blood distribution ratio of AEFP at 96 hours after injection is about 20 times higher than it of Endo at one hour after injection. In conclusion, these studies demonstrate that the anti-cancer or suppression of angiogenesis effect of Endo may be improved by the use of AEFP because the longer half life and stability of AEFP is able to selectively target antigens expressed on tumors.

• 한국환경보건학회지
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• 제23권1호
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• pp.81-94
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• 1997

The concentrations of cadmium, metallothionein(MT), superoxide dismutase(SOD), and lactate dehydrogenase(LDH) were investigated in liver and kidney of rats which were fed the water containing 50 or 100ppm cadmium chloride with basal diet(group A), 5% horsetail diet(group, B), 5% mugwort diet(group C) and 5% champignon diet(group D) for weeks. Cadmium in liver decreased for the first 12 weeks of treatment, but thereafter increased, and was lower in experimental group B,C,D than in control group A. Cadmium in kidney increased linearly during the 16 weeks of treatment, and was lower in group B than in group A. MT in liver decreased for the first 12 weeks of treatment in group A, but increased linearly during the 16 weeks in group B,C,D, higher in group B than in group A. There were significantly higher accumulation of cadmium and MT in liver than in kidney in the beginning of cadmium treatment, but reversed in the ending of treatment. The SOD and LDH activities were not affected during the 16 weeks treatment, and there was no significant difference between groups. Histologic examination revealed moderate to severe hepatic and renal injury in group A compared to horsetail diet group B. These results indicate that the kidney is a major target organ of chronic cadmium poisoning, and suggest that Cd-induced hepatic injury, via release of Cd-MT, may play an important role in the nephrotoxicity. In addition, higher MT concentrations in liver and kidney in the group B constitute a plausible explanation of the protective effects of horsetail diet against the cadmium toxicity in relation to histologic findings.

• 한국응급구조학회지
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• 제10권1호
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• pp.51-60
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• 2006

Background: The toxicity of paraquat has been known to be caused by oxygen free radicals which leads to the lipid peroxidation and multiple organ failure. High dose vitamin C has been known to be a effective antioxidant activities against the paraquat intoxication. This study was designed to evaluate the effect of regular injection of high dose vitamin C on liver damage in paraquat poisoned rat model. Method: Fifty five rats of Sprague-Dawley strain were divided into three groups: control group, only intraperitoneally injected saline; paraquat group, single dose intraperitoneally injected paraquat(24.5%, 40 mg/kg) and every 8 hours injected saline; paraquat and vitamin C group, single dose intraperitoneally injected paraquat(24.5%, 40 mg/kg) and every 8 hours injected vitamin C(72 mg/kg). Rats were sacrificed on the 12 hours, 1st day, 2nd day, 4th day, 7th day after injection and liver tissue was obtained. H&E(Hematoxylin & Eosin) stain and Masson's trichrome stain for collagen fiber detection were undertaken. The results were observed using the microscope. Results: 1. There were no differences between control and experimental group at the 12hours after regular injection of high dose vitamin C. 2. There were significantly decreased liver damage in experimental group in the 1st day after regular injection of high dose vitamin C. 3. There were significantly increased recovery of liver damage with time in experimental group after regular injection of high dose vitamin C. Conclusion: These results suggest that regular injection of high dose vitamin C is effective in decreasing liver damage in paraquat intoxication.

• 대한예방한의학회지
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• 제12권1호
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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.

• 대한약침학회지
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• 제19권2호
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• pp.114-121
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• 2016

Objectives: Lung cancer remains a deadly disease with unsatisfactory overall survival. Cisplatin, a standard platinum (Pt)-based chemotherapeutic agent, has the potential to inhibit the growth of lung cancer. Its use, however, is occasionally limited by severe organ toxicity. However, until now, no systematic study has been conducted to verify its efficacy with proper experimental support in vivo. Therefore, we examined whether biosynthesized Pt nanoparticles (NPs) inhibited human lung cancer in vitro and in vivo to validate their use in alternative and complementary medicine. Methods: We evaluated the in vitro and the in vivo anticancer efficiencies of biosynthesized Pt NPs in a subcutaneous xenograft model with A549 cells. Severe combined immune deficient mice (SCID) were divided into four groups: group 1 being the vehicle control group and groups 2, 3 and 4 being the experimental groups. Once the tumor volume had reached $70-75mm^3$, the progression profile of the tumor growth kinetics and the body weights of the mice were measured every week for 6 weeks after oral administration of Pt NPs. Doses of Pt NPs of 500, 1,000 and 2,000 mg/kg of body weight were administered to the experimental groups and a dose of honey was administered to the vehicle control group. The efficacy was quantified by using the delay in tumor growth following the administration of Pt NPs of A549 human-lung-cancer xenografts growing in SCID mice. Results: The in vitro cytotoxicity evaluation indicated that Pt NPs, in a dose-dependent manner, inhibited the growth of A549 cells, and the in vivo evaluation showed that Pt NPs at the mid and high doses effectively inhibited and delayed the growth of lung cancer in SCID mice. Conclusion: These findings confirm the antitumor properties of biosynthesized Pt NPs and suggest that they may be a cost-effective alternative for the treatment of patients with lung cancer.

• Environmental Analysis Health and Toxicology
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• 제25권2호
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• pp.111-120
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• 2010

DEPs (diesel exhaust particles) like any other particles can be also inhaled into lung to participate in a damaging reaction to the organ. Possible damages might be apoptosis and inflammatory responses to the cells in respiratory track. The aim of this study was cytotoxicity evaluation of DEPs from five in-use diesel vehicles using a murine macrophage cell (RAW 254.7). We found that most DEPs have a considerable cytotoxicity compared to the control and SRM 2975. When measured by MTT assay and extents of apoptosis, DEPs of two highmileage vehicles had higher toxicity than those of the other three low-mileage vehicles tested. Although mRNA expression level of TNF-${\alpha$ somewhat explains the trend of cytotoxicity and apoptosis, that of IL-1$\beta$ did not. Correlation studies among the extents of MTT assay, apoptosis, and TNF-$\alpha$ expression showed that the extents between apoptosis and TNF-$\alpha$ expression was most highly correlated (r=0.96). These results suggest that cytotoxicity of various DEPs could be compared easily by measuring the extent of apoptosis or TNF-$\alpha$ expression by DEPs.