• 대한수의학회지
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• 제44권4호
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• pp.507-513
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• 2004

Aflatoxins are produced mainly by Aspergillus flavus and Aspergillus parasiticus that grow in improperly stored cereals. Aflatoxin B1 ($AFB_1$) is a potent hepatocarcinogen in a variety of experimental animals including human beings. In spite of a high attention to the hepatocarcinogenecity of $AFB_1$, the relative toxicity of aflatoxins ($AFB_2$ and $AFG_1$) is not fully clarified. Sprague-Dawley male rats were orally administered with $AFB_1$, $AFB_2$, and $AFG_1$ at the dose of 250 ${\mu}g/kg$ (additionally including a dose of $1250{\mu}g/kg $ for $AFB_1$) body weight. Animals were then killed at 12, 24 or 48 hrs following aflatoxin exposure. Subsequently the immunohistochemical examination of p53, cytochrome p450 1A1 (CYP450 1A1), and glutathione-S-transferase placental form (GST-P) were performed. The level of the 8-OxodG in the liver was determined. Expressions of CYP450 1A1 and p53 were high in the liver of rats through 48 hrs after treatment of $AFB_1$ at the single dose of $250{\mu}g/kg $. This pattern was more clear as increasing doses. The treatment of $AFB_2$ and $AFG_1$ did not affect the expression of CYP450 1A1 but it caused weak expression of p53. The activity of GST were not found in the liver of rats treated with aflatoxins. The formation of 8-OxodG by $AFB_1$ increased in a dose-dependent manner up to 24 hrs after a single treatment of $AFB_1$ thereafter decreased to the level of control. The treatment of $AFB_2$ and $AFG_1$ did not affect the levels of 8-OxodG in the liver of rats with increasing time. These results in the present study indicate that $AFB_1$ among aflatoxins with low comparable levels is the most toxic as determined by early biomarkers such as CYP450 1A1, p53, GST-P, and 8-OxodG.

• 문화기술의 융합
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• 제4권2호
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• pp.161-169
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• 2018

본 연구는 해조 다당류 추출물을 화장품 원료로 사용할 수 있는지 평가하고자 하였다. 항균 효과를 평가하기 위해 해조 다당류 추출물로 부터 Staphylococcus aureus (S. aureus) 균주에 대한 항균활성을 측정하였다. 또한, RAW 264.7 세포에서 항염증 효과가 확인되었으며, 해조 다당류 추출물을 Sprague-Dawley (SD) 흰쥐의 등쪽 피부에 적용하여 단회투여독성을 평가하였다. 그 결과, 해조 다당류 추출물은 피부섬유 아세포에서 최대 $1,000{\mu}g/mL$ 농도에서 세포 독성을 나타내지 않았다. 또한, 1 % 해조 다당류 추출물로 처리되었을 때, $1.52{\pm}0.34cm$로 생육저해환이 형성되어 S. aureus 균주에 대한 항균 활성을 확인하였다. 해조 다당류 추출물을 RAW 264.7 세포에 처리하면 농도 의존적으로 산화 질소 (NO)의 생성이 감소하고 인터루킨 1 베타 ($IL1{\beta}$), 종양 괴사 인자 알파 ($TNF{\alpha}$)와 같은 염증 관련 사이토카인의 생성이 증가하였으며, 프로스타글란딘 E2 (PGE2)가 감소 하였다. 해조 다당류 추출물을 여러 농도로 흰쥐에 투여했을 때 증상은 14 일 이상 변하지 않았으며 췌장이나 장기 무게에는 변화가 없었다. 결론적으로 우리는 해조 다당류 추출물이 세포 독성을 나타내지 않았으며 항균 및 항염증 효과가 있음을 발견하였다. 따라서, 화장품 원료로 사용하기에 적합하다고 사료된다.

• Journal of Ginseng Research
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• 제23권4호
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• pp.222-229
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• 1999

본 연구는 웅성 기니픽에 있어 2,3,7,8-tetrachlorod-ibenzolp-dioxin(TCDD)-유도 급성독성에 대한 홍삼의 방어효과를 병리조직학적 관찰을 통하여 밝히고저 수행되었다. 40마리의 기니픽($200{\pm}20g$)은 목적에 따라 4군으로 나누었다. 즉, 시험군 1에 대하여는 TCDD의 운반체(미량의 DMSO와 소량의 아세톤을 함유한 대두유)와 생리식염수를, 시험군 2에 대하여는 TCDD와 생리식염수를 복강 주사하였다. 시험군 3(TCDD투여 7일전부터 14일간 투여)과 4(동시투여군, 7일간)에 대하여는 홍삼 물추출물(KRG-WE)을 200mg/kg b.w./day 용량으로 복강주사 하였다. 한편, TCDD($5{\mu}g/kg$ b.w.)는 1회 복강주사 함으로서 급성독성을 유도하였다. 시험군 2에서는 장기의 무게가 현저히 감소하였으며, 특히 간(p<0.05)과 고환(p<0.05), 신장, 비장 및 폐의 무게는 시험군 1 비하여 유의하게 낮았다. 흥선은 심하게 위축되어 있어 지방조직과 구별하기 어려웠다. 폐조직에 있어서는 간질의 미만성화와 섬유아세포의 출현, 간세포의 펭윤, 비장세포에 있어서는 헤모시더린에 침착된 대식세포의 수적 증가, 고환의 정세관에서는 정자 생성 저하 및 세포의 변성이 관찰되었으며, 신장조직에 있어서도 심한 병변이 관찰되었다. 반면, 홍삼 물추출물의 전 혹은 동시 투여군에 있어서는 TCDD-단독 투여군에서 관찰되었던 병리조직학적 소견이 현저히 개선되었다. 특히, TCDD-투여로 야기되는 고환의 위축은 유의하게 억제된다는 사실을 알았다(p<0.01). 이상의 결과는 홍삼 물추출물이 TCDD투여로 야기되는 장기의 조직 손상을 현저히 방어한다는 사실을 시사한다 하겠다.

• Fisheries and Aquatic Sciences
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• 제23권9호
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• pp.26.1-26.9
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• 2020

Background: The study evaluated the effects of a butaphosphan and cyanocobalamin mixture on the immune system and stress in olive flounders, Paralichthys olivaceus. Methods: The mixture was intramuscularly injected into olive flounders at the current recommended dose. Furthermore, to determine the toxicity of overdose, a histological examination was performed after injection of 1-, 2-, and 4-fold higher than the recommended dose. Results: Immunity parameters were altered during the first 2 weeks after a single intramuscular injection of the mixture in olive flounders (average weight 20.5 ± 1.1 g). The levels of all tested items, except glutathione and antiprotease, were higher in the treated group than in the control group in the first week; the levels of all tested items were even higher in the second week in the treated group than in the control group. The level of nitro-blue tetrazolium, myeloperoxidase, and superoxide dismutase between the two groups differed significantly. Changes in the stress response to different seawater temperatures (increase or decrease in seawater temperature by 3-5 ℃ using 50 L heated or cooled seawater tanks) were studied by determining the changes in cortisol and glucose levels on days 1 and 7. Both cortisol and glucose levels were significantly lower in the treated group than in the control group. Histological analysis did not reveal any abnormalities after intramuscular injection of the mixture at doses that were 1-, 2-, and 4-fold higher than the recommended dose. Conclusions: Intramuscular injection of a butaphosphan and cyanocobalamin mixture is safe and effective in reducing stress and improving immunity in olive flounders.

• Toxicological Research
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• 제29권1호
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• pp.53-60
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• 2013

Studies on milk transfer of drugs in non-human primates (NHPs) are among the crucial components in the assessment of peri- and postnatal toxicity because of the similarity between NHPs and humans. To evaluate the milk transfer of valproic acid (VPA) in NHPs, the toxicokinetics of VPA, an antiepileptic drug, were studied in pregnant cynomolgus monkeys. VPA was administered once daily to pregnant cynomolgus monkeys at doses of 0, 30, 90, and 270 mg/kg by oral gavage from Day 100 of gestation (GD 100) to Day 31 of lactation (LD 31). Concentrations of VPA and its metabolite, 4-ene-VPA, in the maternal plasma on GD 100, GD 140, and LD 30, and concentrations of VPA and 4-ene-VPA in the offspring plasma and milk on LDs 30 and 31, respectively, were quantified using liquid chromatography tandem mass spectrometry (LC/MS/MS). After administration of a single oral dose of VPA to pregnant monkeys on GD 100, the concentrations of VPA and 4-ene-VPA were generally quantifiable in the plasma of all treatment groups up to 24 hr after administration, which showed that VPA was absorbed and that the monkeys were systemically exposed to VPA and 4-ene-VPA. After administration of multiple doses of VPA to the monkeys, VPA was detected in the pup's plasma and in milk taken on LD 30 and LD 31, respectively, which showed that VPA was transferred via milk, and the pup was exposed to VPA. Further, the concentration of VPA in the milk increased with an increase in the dose. Extremely low concentrations of 4-ene VPA were detected in the milk and in the pup plasma. In conclusion, pregnant monkeys were exposed to VPA and 4-ene-VPA after oral administration of VPA at doses of 30, 90, and 270 mg/kg/day from GD 100 to LD 31. VPA was transferred via milk, and the VPA exposure to the pup increased with an increase in the dose of VPA. The metabolite, 4-ene VPA, was present in extremely low concentrations (< 0.5 ${\mu}g/ml$) in the milk and in the pup plasma. In this study, we established methods to confirm milk transfer in NHPs, such as mating and diagnosis of pregnancy by examining gestational sac with ultrasonography, collection of milk and pup plasma and determination of toxicokinetics, using cynomolgus monkeys.

• Toxicological Research
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• 제22권2호
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• pp.75-85
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• 2006

This study was designed to evaluate the possible DNA damaging effects of T-2 toxin using an alkaline single cell gel electrophoresis (SCGE) comet assay and also to investigate toxic effects in chickens. A total of 20 chickens were used in these experiments. Graded concentrations of dietary T-2 toxin (0, 4, 8, and $16{\mu}g/g$ of diet) were given to groups of 5 broiler chickens. In comet assay, The DNA damage was analysed by the tail extent moment (TEM) and tail length (TL), which were used as markers of DNA strand breaks in SCGE. A significant dose-dependent increase in the extent of DNA migration as well as in the percentage of cells with tails was observed after treatment with T-2 toxin (P<0.05). Treatment with the low T-2 toxin ($4{\mu}/g$ of diet) induced a relatively low level of DNA damage in comparison with the high T-2 toxin ($16{\mu}/g$ of diet) group. The growth rate was significantly reduced by concentrations of 8, and $16{\mu}/g$ of diet (P < 0.05). The feed conversion ratio were significantly affected by any concentrations (P < 0.05). The relative weight of the spleen, and lung was decreased by the growth inhibitory concentrations. The bursa of Fabricius, thymus, and kid- ney were decreased in relative weight by concentrations of $16{\mu}/g$ of diet. The relative weight of the liver and heart were unaffected. The hemoglobin (Hb), hematocrit (HCT), and mean corpuscular hemoglobin (MCH) were decreased at concentration of $16{\mu}/g$ of diet. As compared with control chickens, there was no marked change in serum components except uric acid in T-2 treated chickens. All lymphoid tissues retained atrophic and lymphoid cell depletion throughout the three weeks trial.

• Radiation Oncology Journal
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• 제33권4호
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• pp.310-319
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• 2015

Purpose: Follicular lymphoma (FL) is an indolent non-Hodgkin's lymphoma that is highly sensitive to radiotherapy (RT). However, the effectiveness of RT has not been well established. We reviewed our experiences to assess the role of RT for FL and analyze treatment results. Materials and Methods: Retrospective analysis was done on 29 patients who received first RT between January 2003 and August 2013. Of 23 early stage (stage I, II) patients, 16 received RT alone, four received chemotherapy followed by RT, two received RT postoperatively, and one received salvage RT for relapse after resection. Six advanced-stage (stage III, IV) patients received RT after chemotherapy: two received consolidation RT, three received salvage RT for residual lesions, and one received RT for progressive sites. Median RT dose was 30.6 Gy (range, 21.6 to 48.6 Gy). Median follow-up duration was 62 months (range, 6 to 141 months). Results: All patients showed complete response in the radiation field. Eight outfield relapses were reported. Seven patients received salvage treatment (three chemotherapy, four RT). Four patients showed excellent responses, especially to RT. Estimated 5-year and 10-year relapse-free survivals were 72% and 60%. In the RT-alone group, 5-year relapse-free survival was 74.5%. All advanced-stage patients were disease-free with 100% 5-year overall survival. Disease-specific death was noted in only one patient; four others died of other unrelated causes. No significant toxicity was reported. Conclusion: RT resulted in excellent treatment outcomes for all FL stages when used as a primary treatment modality for early stage or salvage-treatment modality for advanced-stage disease.

• 대한수의학회지
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• 제16권1호
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• pp.59-64
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• 1976

In the sequence of carbon tetrachloride hepatotoxicity, increased serum levels of a number of enzymes have been demonstrated in experimental animals. These observations, therefore, have served to help in detecting hepatic injury. The serological influence of chlorpromazine (CPZ) and iproniazid on the acute $CCl_4$ poisoning was executed in this investigation taking use of 6 albino rabbits (around 2 kg b.w.) in each group. By measuring of blood sugar level (Nelson-Somogyi method), S-GOT and S-GPT activities (Reitman-Frankel method), the pharmacological effects of the drugs was evaluated setting pretreated groups against the control. The results obtained were summarized as follows: 1. The intramuscular injection of $CCl_4$ led to increase the blood sugar level in first 3 hours and, after that, to decrease reasonably. But CPZ-pretreated group showed a tendency of increasing in compare with the control, and iproniazid-pretreated group inhibited evidently. 2. In S-GOT activity, the increased level was induced by $CCl_4$ in control. And CPZ-pretreated group showed a increased level until first day and decreased rapidly. But this property inhibited inhibited significantly by pretreating with iproniazid. 3. Although a single dose of $CCl_4$ increased the S-GPT activity, the more increasing trend was observed in CPZ-pretreated group. But these tendencies depressed remarkably in the iproniazid-pretreated group. It seemed to be attributed not to defend the $CCl_4$ toxicity but to be suppressed the enzyme systems in the liver by iproniazid that the blood sugar level and serum transaminase activities was decreased significantly in pretreating with iproniazid.

• 혜화의학회지
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• 제22권1호
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• pp.119-128
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• 2013

Objectives: Yijin-tang-gamibang has been used in the Korean Medicine for treating various digestive disease. This study was aimed to investigate the effects and safety of Yijin-tang-gamibang in reflux esophagitis through the analysis of articles. Method: A total of 9 articles about Yijin-tang-gamibang and reflux esophagitis were used to develop this article. Results: According to basic research and clinic research data, it is supported that Yijin-tang-gamibang was useful prescription in reflux esophagitis. Yijin-tang-gamibang has favorable protective effects on the reflux esophagitis induced by pylorus and forestomach ligation in rats. After treatment with Yijin-tang-gamibang, patients showed improvement in all symptoms associated with reflux esophagitis and functional dyspepsia, including general condition. And Yijin-tang-gamibang did not show any toxic effect in single oral dose toxicity test. Conclusion: The results of this study suggest that Yijin-tang-gamibang showed favorable protective effects on the reflux esophagitis. However, it proved insufficient to confirm its efficacy owing to lack of clinical studies of high quality. So, we need well designed studies to verify clinical efficacy of Yijin-tang-gamibang hereafter.

• BMB Reports
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• 제36권4호
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• pp.373-378
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• 2003

Effects of L-arginine and NG-nitro-L-arginine methyl ester (L-NAME) on the renal dysfunction that is induced by cisplatin (CDDP) were investigated. A single dose of CDDP (7.5 mg/kg i.p.) induced renotoxicity, which was manifested by increasing the sensitivity of isolated urinary bladder rings to acetylcholine (ACh), together with a significant elevation of serum urea and creatinine, and a severe decrease in serum albumin. Moreover, renal dysfunction was further confirmed by a significant decrease of enzyme activities, such as glutathione peroxidase, GSH-Px (E.C 1.11.1.9), catalase (E.C 1.11.1.6), as well as a significant increase in lipid peroxides that were measured as malondialdhyde (MDA) in kidney tissue homogenates. The administration of L-arginine (70 mg/kg/d p.o in drinking water 5 d before and 5 d after the CDDP injection) significantly ameliorated the renotoxic effects of CDDP, as judged by restoring the normal responses of isolated bladder rings to Ach, and also by an improvement in a range of renal function indices, which included serum urea and creatinine concentrations and kidney weight. In addition, L-arginine prevents the rise of MDA, as well as a reduction of GSH-Px and catalase activities in kidney tissues homogenates. On the other hand, the administration of L-NAME (4 mg/kg/d p.o) resulted in no protection against renal dysfunction that was induced by CDDP treatment. The findings of this study suggest that L-arginine can attenuate kidney injury that is produced by CDDP treatment. In addition, L-arginine may be a beneficial remedy for CDDP-induced renal toxicity, and could be used to improve the therapeutic index of CDDP.