• 대한약침학회지
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• 제22권3호
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• pp.147-153
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• 2019

Objectives: Many studies have been reported the efficacy of intravenous lipid emulsion (ILE) as an antidote on acute lipophilic drug toxicity. Clozapine, highly lipophilic dibenzodiazepine neuroleptics, is an important medication in the schizophrenia therapy regimen. Acute intoxication with antipsychotics is one of the main reasons for the referral of poisoned patients to the hospital. We expected that ILE could be used for the therapy of acute clozapine intoxicated patients. Methods: We used two groups of consisting of six male rats. Both groups received a toxic dose of clozapine (40 mg/kg) intravenously, via the tail vein. After 15 minutes, they were treated with intravenous infusion of 18.6 mg/kg normal saline (NS group), or 18.6 mg/kg ILE 20% (ILE group). We evaluated blood pressure (BP) and heart rate by power lab apparatus through the tail artery, ataxia by a rat rotary circle, seizure scores and death in multiple times after starting clozapine administration. For biochemical and pathological evaluations the samples of tissue and blood were taken. Results: Our results demonstrated that ILE 20% could return hypotension-induced clozapine better than normal saline. Furthermore, ataxia and seizure have rectified more rapidly and deaths reduced. Clozapine administration causes pancreatitis and lung injury but fat emulsion did not show an optimal effect on tissue damages caused by clozapine toxicity. Conclusion: In conclusion, ILE can remove toxic signs of clozapine same as other lipophilic medicines, however, clinical uses of ILE for this intention requires more appraisement to determine the precise implication and safety.

• Journal of Microbiology and Biotechnology
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• 제31권2호
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• pp.290-297
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• 2021

Leptolyngbya sp. KIOST-1 (LK1) is a newly isolated cyanobacterium that shows no obvious cytotoxicity and contains high protein content for both human and animal diets. However, only limited information is available on its toxic effects. The purpose of this study was to validate the safety of LK1 powder. Following Organisation for Economic Co-operation and Development (OECD) guidelines, a single-dose oral toxicity test in Sprague Dawley rats was performed. Genotoxicity was assessed using a bacterial reverse mutation test with Salmonella typhimurium (strains TA98, TA100, TA1535, and TA1537) and Escherichia coli WP2 uvrA, an in vitro mammalian chromosome aberration test using Chinese hamster lung cells, and an in vivo mammalian erythrocyte micronucleus test using Hsd:ICR (CD-1) SPF mouse bone marrow. After LK1 administration (2,500 mg/kg), there were no LK1-related body weight changes or necropsy findings. The reverse mutation test showed no increased reverse mutation upon exposure to 5,000 ㎍/plate of the LK1 powder, the maximum tested amount. The chromosome aberration test and micronucleus assay demonstrated no chromosomal abnormalities and genotoxicity, respectively, in the presence of the LK1 powder. The absence of physiological findings and genetic abnormalities suggests that LK1 powder is appropriate as a candidate biomass to be used as a safe food ingredient.

• Tuberculosis and Respiratory Diseases
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• 제47권1호
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• pp.77-89
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• 1999

연구 배경: 고위험군의 악성 질환의 치료로 최근에 시도되고 있는 고용량 항암화학요법은 기존의 치료보다 치료 반응율이 높고 생존의 향상을 기대할수 있는 방법이다. 그러나 치료와 관련된 부작용도 있어 이환율 및 사망률도 높다. 말초 조혈모세포이식을 이용한 고용량 항암화학요법 후에 발생하는 특발성 폐렴 증후군은 감염성 원인을 배제한다면 약제에 의한 폐독성으로 유발되었을 가능성이 가장 높다. 저자들은 약제 독성으로 유발되었을 것으로 추정되는 폐렴 증후군에 대하여 알아보고자 하였다. 방법: 1995년 5월부터 1997년 12월까지 아주대학교병원에서 말초 조혈모세포이식을 이용한 고용량 항암화학 요법을 시행받은 환자들을 대상으로 하였다. 이들 중 특발성 폐렴 증후군이 발생한 5례에서 경기관지폐생검을 시행하고 그 임상 양상과 치료 결과를 후향적으로 분석하였다. 결과: 전체 대상 환자는 97례이었으며 이들중 5례(5.1%)에서 특발성 폐렴 증후군이 발생하였다. 5례의 환자의 연령은 평균 $41{\pm}13$세, 남녀비는 3:2였으며 유방암 3례, 악성 림프종 2례이었다. 사용된 항암제는 CBP regimen 3례, BEAC regimen 1례, BEAM regimen 1례이었으며, 사용된 용량은 BCNU 300-400 mg/$m^2$, cyclophosphsmide 6,000 mg/$m^2$이었다. 다섯 례 모두에서 고용량 항암화학요법 전에 방사선 치료를 받았다. 고용량 항암화학요법을 시행한지 평균 14주 후 (4-26주)에 기침, 호흡곤란, 발열 등을 동반한 폐침윤이 발생하였다. 흉부 방사선 검사 소견상 3례에서는 양측성, 2례에서는 우하엽에 국한된 미만성의 폐침윤을 보였다. 경기관지폐생검 결과 폐포 손상과 격막의 비후, 비정상적인 제 II 형 폐세포의 증식이 관찰되었고 악성 세포의 침윤이나 감염성 질환 등의 소견은 없었다. 모든 환자에서 스테로이드를 투여하였으나 2례에서는 급성 호흡부전증으로 진행하여 사망하였다. 3례에서는 폐병변이 소실되고 중상도 호전되었으나 1례는 확장성 심근병으로 사망하였고 2례는 호전되어 폐병변이 없는 상태에서 외래 관찰 중이다. 결론: 말초 조혈모세포이식을 이용한 고용량 항암화학요법은 치료 효과가 기존의 항암치료보다 높지만 BCNU를 포함하는 복합 화학요법을 사용하는 경우 약제에 폐손상이 발생할 가능성이 있어 적절한 환자의 선정과 폐손상을 최소화할 수 있도록 유의하여야 한다.

• Asian Pacific Journal of Cancer Prevention
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• 제13권11호
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• pp.5887-5895
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• 2012

Background: To determine the effect of essential oil obtained from a traditionally used medicinal plant Tridax procumbens L, on lung metastasis developed by B16F-10 melanoma cells in C57BL/6 mice. Materials and Methods: Parameters studied were toxicity, lung tumor nodule count, histopathological features, tumor directed capillary vessel formation, apoptosis and expression levels of $P^{53}$ and caspase-3 proteins. Results: In vitro the MTT assay showed cytotoxicity was found to be high as 70.2% of cancer cell death within 24hrs for $50{\mu}g$. In vivo oil treatment significantly inhibited tumor nodule formation by 71.7% when compared with untreated mice. Formation of tumor directed new blood vessels was also found to be inhibited to about 39.5%. TUNEL assays also demonstrated a significant increase in the number of apoptotic positive cells after the treatment. $P^{53}$ and caspase-3 expression was also found to be greater in the essential oil treated group than the normal and cancer group. Conclusions: The present investigation showed significant effects of the essential oil of Tridax procumbens L in preventing lung metastasis by B16F-10 cell line in C57BL/6 mice. Its specific preventive effect on tumor directed angiogenesis and inducing effect on apoptosis warrant further studies at the molecular level to validate the significance of Tridax procumbens L for anticancer therapy.

• 한국환경성돌연변이발암원학회지
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• 제21권1호
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• pp.14-22
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• 2001

The detection of many synthetic chemicals used in industry that may pose a genetic hazard in our environment is of great concern at present. In this respect, administrative authorities has great concern to regulate and to evaluate the chemical hazard to environment and human health. The clastogenicity of 28 synthetic chemicals was evaluated in Chinese hamster lung fibroblast cells in vitro. Glycidylacrylate which is one of the most cytotoxic chemical among 28 chemicals tested revealed clastogenicity in the range of 0.31-1.25 $\mu\textrm{g}$/$m\ell$ both in the presence and absence of metabolic activation system. Neopentyl glycol (340-1360 $\mu\textrm{g}$/$m\ell$) also revealed weak positive result both in the presence and absence of metabolic activation system. Cyanoguanidine (/$420.5-841 $\mu\textrm{g}$m\ell$) and N-butylchloride ($231.5-926 $\mu\textrm{g}$/m\ell$) revealed weak positive result only in the absence of S-9 metabolic activation system. Nevertheless total aberration percentages of N-butylchloride in the presence of metabolic activation system, and 3,4＇-dichlorobenztrifluoride in the absence of S-9 metabolic activation revealed above 5% aberration, there is no statistical significance. From the results of chromosomal aberration assay with 28 synthetic chemicals in Chinese hamster lung cells, glycidylacrylate (CAS No. 106-90-0), neopentyl glycol (CAS No. 126-30-7), N-butyl chloride (CAS No. 109-69-3) and cyanoguanidine (CAS No. 461-58-5) revealed positive clastogenic results in this study.

• 한국환경성돌연변이발암원학회지
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• 제22권4호
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• pp.215-222
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• 2002

The detection of many synthetic chemicals used in industry that may pose a genetic hazard in our environment is of great concern at present. Since these substances are not limited to the original products, and enter the environment, they have become widespread environmental pollutants, thus leading to a variety of chemicals that possibly threaten the public health. In this respect, to regulate and to evaluate the chemical hazard will be important to environment and human health. The clastogenicity of 17 synthetic chemicals was evaluated in Chinese hamster lung fibroblast cells in vitro. Two most cytotoxic chemicals, dodecyl methacrylate (CAS No. 142-90-5) and 2-ethylhexyl methacrylate (CAS No. 688-84-6), among 17 chemicals tested revealed no clastogenicity in the range of 0.0165-0.066 $\mu\textrm{g}$/$m\ell$ and 0.006-0.024 $\mu\textrm{g}$/$m\ell$ both in the presence and absence of metabolic activation system, respectively. All 17 chemicals revealed no significant induction of chromosomal aberration both in the presence and absence of metabolic activation system in this assay. From the results of chromosomal aberration assay with 17 synthetic chemicals in Chinese hamster lung cells in vitro, we did not observed positive clastogenic results in this study.

• Biomolecules & Therapeutics
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• 제28권3호
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• pp.250-258
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• 2020

Emphysema, a major component of chronic obstructive pulmonary disease (COPD), is a leading cause of human death worldwide. The progressive deterioration of lung function that occurs in the disease is caused by chronic inflammation of the airway and destruction of the lung parenchyma. Despite the main impact of inflammation on the pathogenesis of emphysema, current therapeutic regimens mainly offer symptomatic relief and preservation of lung function with little therapeutic impact. In the present study, we aimed to discover novel therapeutics that suppress the pathogenesis of emphysema. Here, we show that LJ-2698, a novel and highly selective antagonist of the adenosine A₃ receptor, a G protein-coupled receptor involved in various inflammatory diseases, significantly reversed the elastase-induced destructive changes in murine lungs. We found that LJ-2698 significantly prevented elastase-induced airspace enlargement, resulting in restoration of pulmonary function without causing any obvious changes in body weight in mice. LJ-2698 was found to inhibit matrix metalloproteinase activity and pulmonary cell apoptosis in the murine lung. LJ-2698 treatment induced increases in anti-inflammatory cytokines in macrophages at doses that displayed no significant cytotoxicity in normal cell lines derived from various organs. Treatment with LJ-2698 significantly increased the number of anti-inflammatory M2 macrophages in the lungs. These results implicate the adenosine A₃ receptor in the pathogenesis of emphysema. Our findings also demonstrate the potential of LJ-2698 as a novel therapeutic/preventive agent in suppressing disease development with limited toxicity.

• Asian Pacific Journal of Cancer Prevention
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• 제16권6호
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• pp.2307-2312
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• 2015

Curcumol is a sesquiterpene originally isolated from curcuma rhizomes, a component of herbal remedies commonly used in oriental medicine. Its beneficial pharmacological activities have attract significant interest recently. In this study, anti-cancer activity of curcumol was examined with both in vitro and in vivo models. It was found that curcumol exhibited time- and concentration-dependent anti-proliferative effects in SPC-A-1 human lung adenocarcinoma cells with cell cycle arrest in the G0/G1 phase while apoptosis-induction was also confirmed with flow cytometry and morphological analyses. Interestingly, curcumol did not display growth inhibition in MRC-5 human embryonic lung fibroblasts, suggesting the anti-proliferative effects of curcumol were specific to cancer cells. Anti-neoplastic effects of curcumol were also confirmed in tumor bearing mice. Curcumol (60 mg/ kg daily) significantly reduced tumor size without causing notable toxicity. In conclusion, curcumol appears a favorable anti-cancer candidate for further development.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1993년도 제2회 신약개발 연구발표회 초록집
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• pp.74-74
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• 1993

The in vitro cytotoxicity of SKI 2053R was evaluated against human tumor cell lines along with those of cisplatin and carboplatin using MTT assay. The cell lines tested were two human lung cancer cell lines and five human stomach cancer celt lines. The level of cytotoxic effects of SKI 2053R against two human lung cancer cell lines was located between cisplatin and carboplatin. However, the cytotoxic activity of SKI 2053R against five human stomach cancer cell lines was similar to that of cisplatin. SKI 2053R is considered to be selectively cytotoxic toward human stomach cancer cell lines. We carried out pharmacokinetic and ex vivo phrmacodynamic studies of SKI 2053R in beagle dogs to predict the clinical antitumor effect of SKI2053R, comparing with those of cisplatin and carboplatin. In ex vivo pharmacodynamics which used MTT assay as bioassay on the 2 lung and 5 stomach cancer cell, mean antitumor indexes (ATIs) of SKI 2053R were highest among three compounds in both lung and stomach cancer cell lines, especially in stomach cancer cell. Much higher ATI profile and maximal inhibition rates of SKI 2053R appeared in the stomach cancer cells will give desirable advantages to clinical trial s against gastric carcinoma. The anti tumor activity and target organ toxicity of SKI 2053R were compared with those of cisplatin on stomach cancer cell line, KATO III xenografted into nude BALB/c(nu/nu) mice. All groups of cisplatin and SKI 2053R showed active tumor regression. The inhibition rates(IR) of SKI 2053R were higher than that of cisplatin on the basis of mean IR. Though the loss of body weight was observed in all groups from the first week, the SKI 2053R group recovered it soon from the third week after the initiation of treatment, maintaining the most active anti tumor activity among three groups.

• Genomics & Informatics
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• 제20권3호
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• pp.29.1-29.12
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• 2022

Several studies have shown associations between irinotecan toxicity and UGT1A genetic variations in colorectal and lung cancer, but only limited data are available for gastric cancer patients. We evaluated the frequencies of UGT1A polymorphisms and their relationship with clinicopathologic parameters in 382 Korean gastric cancer patients. Polymorphisms of UGT1A1*6, UGT1A1*27, UGT1A1*28, UGT1A1*60, UGT1A7*2, UGT1A7*3, and UGT1A9*22 were genotyped by direct sequencing. In 98 patients treated with irinotecan-containing regimens, toxicity and response were compared according to the genotype. The UGT1A1*6 and UGT1A9*22 genotypes showed a higher prevalence in Korean gastric cancer patients, while the prevalence of the UG1A1*28 polymorphism was lower than in normal Koreans, as has been found in other studies of Asian populations. The incidence of severe diarrhea after irinotecan-containing treatment was more common in patients with the UGT1A1*6, UGT1A7*3 and UGT1A9*22 polymorphisms than in controls. The presence of the UGT1A1*6 allele also showed a significant association with grade III-IV neutropenia. Upon haplotype and diplotype analyses, almost every patient bearing the UGT1A1*6 or UGT1A7*3 variant also had the UGT1A9*22 polymorphism, and all severe manifestations of UGT1A polymorphism-associated toxicity were related to the UGT1A9*22 polymorphism. By genotyping UGT1A9*22 polymorphisms, we could identify high-risk gastric cancer patients receiving irinotecan-containing chemotherapy, who would experience severe toxicity. When treating high-risk patients with the UGT1A9*22 polymorphism, clinicians should closely monitor them for signs of toxicity such as severe diarrhea or neutropenia.