• 한국정보통신학회:학술대회논문집
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• 한국정보통신학회 2022년도 춘계학술대회
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• pp.273-275
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• 2022

임산부에게 약물을 사용하는 것은 태아에게 잠재적인 위협이 될 수 있으므로 임산부가 복용을 피해야 할 약물을 분류하는 것은 필수적이다. 하지만 많은 화합물이 태아에게 독성을 나타낼 수 있는지에 대한 근거가 불분명하며, 그것을 밝혀내기 위해서는 많은 시간과 비용이 투자된다. In silico 기반 가상 스크리닝은 광범위한 화합물에 대해서 적은 비용과 시간으로 어떤 화합물이 태아에게 높은 위험을 보일 수 있는지 예측하는데 활용될 수 있다. 우리는 한국과 호주 정부의 임신 중 약물 처방을 위한 위험 분류 리스트를 활용해 약물의 분류 등급 정보를 가져왔다. 약물의 구조적 특징과 화학적 특징을 기반으로 다양한 머신 러닝 기법을 적용하여 약물의 태아 독성 여부를 예측하는 모델을 생성하였으며, 정량적 성능 평가를 수행하였다. 나아가, attention 알고리즘을 활용하여 제안하는 모델이 약물의 태아 독성을 예측하는 과정에서 화합물의 어떤 하위 분자 구조가 중요하게 활용되었는지 확인하였다. 해당 연구를 통해 광범위한 화합물에 대해 높은 태아 독성 위험도를 가진 약물을 머신 러닝을 통해 예측할 수 있는 것을 확인하였다. 우리의 연구는 단순한 약물의 태아 독성 예측에서 나아가, 유의미한 하위 분자구조를 제공함으로써 연구자들이 약물의 태아 독성을 증명하기 위해 수행하는 실험에서 핵심적인 역할이 가능할 것이다.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 2008년도 Proceedings of the Convention
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• pp.168-168
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• 2008

• 대한한방내과학회지
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• 제23권2호
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• pp.222-227
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• 2002

Although there are a few reports concerning the side effects and toxicity of herbal medicines, there has not yet been any report concerning their causes, mechanisms or prevention. We investigated the internal reports concerning the side effects and toxicity of herbal medicines. In the findings, liver disorder (hepatic injury) was found in 7 cases, kidney disorders (nephropathy) were found in 12 cases, heart disorders were found in 4 cases and mineral-caused diseases were found in 2 cases. Besides, we found the major cause of the side effects and toxicity was drug abuse, such as over-dosage and long term medication. So, we hope this report brings more attention to the safety and toxicity of herbal medicines.

• 한국자원식물학회지
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• 제27권1호
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• pp.11-21
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• 2014

본 연구는 Atractylodes macrocepala KOIDZ.의 급성 경구 독성을 평가하기 위하여 SD계 Rat를 이용하여 농도별 열수 추출물을 투여하고 체중변화, 이상반응, 장기무게변화, 혈액학적 이상반응, 조직병리학적 이상반응 등을 측정하였다. Atractylodes macrocepala KOIDZ.를 투여한 실험군에서 비교적 낮은 농도에서 체중의 감소가 관찰되었으나, 이상반응이나 장기무게에 있어 유의성 있는 변화는 관찰되지 않았다. 혈액학적 지표에 있어서도 비교적 낮은 농도에서 WBC 및 AST의 증가가 관찰되었다. 조직병리학적 소견에서 일부 간조직의 지방변성이 관찰되어 간독성과 간세포에 미치는 영향에 대한 연구가 필요할 것으로 판단된다. 이와 같은 연구의 결과를 종합해 볼 때 백출이 경구투여에 있어 비교적 안전한 물질인 것으로 판단할 수 있다. 그러나 단회 경구투여 급성독성시험만으로 천연물 생약에 대한 독성 유무를 판단하기에는 일정부분 제약이 있으므로, 추가적으로 2주(또는 4주) 반복 경구투여 독성시험 및 13주 반복 경구투여 독성시험 그리고 유전독성에 대한 연구들이 순차적으로 수행되어야 하며, 이를 통하여 백출에 대한 체계적인 독성정보를 구축함으로써 보다 정확하고 과학적 근거에 입각한 안전성 자료가 확보될 수 있을 것으로 기대한다.

• 생물정신의학
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• 제7권1호
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• pp.3-13
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• 2000

There is nothing that is harmless ; the dose alone decides that something is no poison(Paracelsus, 1493-1541). So, in a point of view to maximize the therapeutic efficacy of drug therapy in a way that minimize the drug toxicity, the knowledges of the drug-ineractions as well as the pharmacokinetic and pharmacodynamic principles of every therapeutic drug used in the medical clinic cannot be emphasized too much. Many drug interactions can be predicted if the pharmacokinetic properties, pharmacodynamic mechanisms of action of the interacting drugs are known, and most adverse interactions can be avoided. In this paper, the clinical importance, classification, and general principles of clinical drug-interactions are presentated with a few explanatory examples.

• 대한한의학회지
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• 제31권3호
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• pp.128-132
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• 2010

Objectives: This study aimed to review the general features of drug induced liver injury (DILI) and the important factors in consideration of herbal drugs and DILI. Methods: We reviewed general aspects of DILI such as classification, inducible factors, diagnosis methods, prevention, and the status of herbal drug-associated DILI via literature. Results: Besides the drug itself, genetic and environmental factors affect hepatic toxicity. There is a lack of definitive diagnoses of DILI by drugs, including herbal remedies. The possibility of herbal drug-associated DILI is exaggerated, and majority of herbal drug-derived hepatic injury could be easily prevented if Oriental doctors pay attention to this issue. Conclusion: This study can provide Oriental doctors an overview and be helpful in minimizing the episodes of hepatotoxicity in use of herbal drugs.

• Toxicological Research
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• 제14권3호
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• pp.427-433
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• 1998

The acute and genetic toxicity of DK1002 was subjected in this study. DK1002 which is a morphine-like new drug candidate synthesized by Dong-Kook Pharmaceutical Co. Ltd. is now under developing as a analgesics that have better drug efficacy and least addictive property. In acute toxicity study, the 50% lethal doses ($LD_{50}$) of DK1002 were determined as>2000mg/kg (p.o.), 237.0mg/kg(i.p.), 57.5mg/kg(i.v.), and 1266.9mg/kg (s.c.). And also, to study the genotoxicity of DK1002, we performed bacterial reversion assay with Salmonella typhimurium TA98, TA100, TA1535, and TA1537, and in vitro chromosomal aberration assay with Chinese hamster lung cells in the presence and absence of S-9 metabolic activation system. In vivo micronucleus assay using mouse bone marrow cells was also performed. From these results, DK1002 was revealed nonmutagenic potential in S. typhimurium TA98, TA100, TA1535, and TA537 both in the absence and presecne of metablic activation system. No clastogenicity of DK1002 was observed in chromosomal aberration assay in vitro as well as in micronucleus assay in vivo.

• Toxicological Research
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• 제22권2호
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• pp.87-93
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• 2006

The KFDA (Korea Food & Drug Administration) has performed a collaborative toxico-genomics project since 2003. Its aim is to construct a toxicologenomic database of 12 hepatotoxic compounds from mice livers. Phenylbutazone which is non-steroidal anti-inflammatory drug was assigned. It was administered at low (0.0238 mg/kg) and at high (0.238 mg/kg) dose (5 mice per group) orally to the postnatal 6 weeks ICR mice, then the serum and liver were collected at the indicated time (6, 24 and 72 h) after administration. Serum biochemical markers for liver toxicity were measured and histopathologic studies also were carried out. The gene expression profiling was carried out by using Applied Biosystems 1700 Full Genome Expression Mouse. The 2-way ANOVA was used to find genes that reflected phenylbutazone-induced acute toxicity or dose-dependant changes. By self-organization maps (SOM), we identified groups with unique gene expression patterns, some of them are supposed to be related to phenylbutazone induced toxicity, including lipid metabolism abnormality, oxidative stress, cell death and cytoskeleton destruction.

• Toxicological Research
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• 제29권4호
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• pp.285-292
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• 2013

Ginseng is a well-known traditional medicine used in Asian countries for several thousand years, and it is currently applied to medicine, cosmetics, and nutritional supplements due to its many healing and energygiving properties. It is well demonstrated that ginsenosides, the main ingredient of ginseng, produce a variety of pharmacological and therapeutic effects on central nerve system (CNS) disorders, cardiovascular disease, endocrine secretions, aging, and immune function. Korean red ginseng extract is a dietary supplement containing ginsenoside Rb1 and ginsenoside Rg1 extracted from Panax ginseng. While the pharmacokinetics and bioavailability of the extract have been well established, its toxicological properties remain obscure. Thus, four-week oral toxicity studies in rats were conducted to investigate whether Korean red ginseng extract could have a potential toxicity to humans. The test article was administered once daily by oral gavage to four groups of male and female Sprague-Dawley (SD) rats at dose levels of 0, 500, 1,000, and 2,000 mg/kg/day for four weeks. Neither deaths nor clinical symptoms were observed in any group during the experiment. Furthermore, no abnormalities in body weight, food consumption, ophthalmology, urinalysis, hematology, serum biochemistry, gross findings, organ weights, or histopathology were revealed related to the administration of the test article in either sex of any dosed group. Therefore, a target organ was not determined in this study, and the no observed adverse effect level (NOAEL) of Korean red ginseng extract was established to be 2,000 mg/kg/day.

• Journal of Dental Anesthesia and Pain Medicine
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• 제19권4호
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• pp.181-189
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• 2019

Local anesthetic systemic toxicity (LAST) refers to the complication affecting the central nervous system (CNS) and cardiovascular system (CVS) due to the overdose of local anesthesia. Its reported prevalence is 0.27/1000, and the representative symptoms range from dizziness to unconsciousness in the CNS and from arrhythmias to cardiac arrest in the CVS. Predisposing factors of LAST include extremes of age, pregnancy, renal disease, cardiac disease, hepatic dysfunction, and drug-associated factors. To prevent the LAST, it is necessary to recognize the risk factors for each patient, choose a safe drug and dose of local anesthesia, use vasoconstrictor, confirm aspiration and use incremental injection techniques. According to the treatment guidelines for LAST, immediate application of lipid emulsion plays an important role. Although lipid emulsion is commonly used for parenteral nutrition, it has recently been widely used as a non-specific antidote for various types of drug toxicity, such as LAST treatment. According to the recently published guidelines, 20% lipid emulsion is to be intravenously injected at 1.5 mL/kg. After bolus injection, 15 mL/kg/h of lipid emulsion is to be continuously injected for LAST. However, caution must be observed for >1000 mL of injection, which is the maximum dose. We reviewed the incidence, mechanism, prevention, and treatment guidelines, and a serious complication of LAST occurring due to dental anesthesia. Furthermore, we introduced lipid emulsion that has recently been in the spotlight as the therapeutic strategy for LAST.