• 한국발생생물학회지:발생과생식
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• 제19권4호
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• pp.167-180
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• 2015

Arsenic is a toxic metalloid that exists ubiquitously in the environment, and affects global health problems due to its carcinogenicity. In most populations, the main source of arsenic exposure is the drinking water. In drinking water, chronic exposure to arsenic is associated with increased risks of various cancers including those of skin, lung, bladder, and liver, as well as numerous other non-cancer diseases including gastrointestinal and cardiovascular diseases, diabetes, and neurologic and cognitive problems. Recent emerging evidences suggest that arsenic exposure affects the reproductive and developmental toxicity. Prenatal exposure to inorganic arsenic causes adverse pregnancy outcomes and children's health problems. Some epidemiological studies have reported that arsenic exposure induces premature delivery, spontaneous abortion, and stillbirth. In animal studies, inorganic arsenic also causes fetal malformation, growth retardation, and fetal death. These toxic effects depend on dose, route and gestation periods of arsenic exposure. In males, inorganic arsenic causes reproductive dysfunctions including reductions of the testis weights, accessory sex organs weights, and epididymal sperm counts. In addition, inorganic arsenic exposure also induces alterations of spermatogenesis, reductions of testosterone and gonadotrophins, and disruptions of steroidogenesis. However, the reproductive and developmental problems following arsenic exposure are poorly understood, and the molecular mechanism of arsenic-induced reproductive toxicity remains unclear. Thus, we further investigated several possible mechanisms underlying arsenic-induced reproductive toxicity.

• 한국식품저장유통학회지
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• 제30권5호
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• pp.797-810
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• 2023

Elaeagnus umbellata leaves have been reported to suppress inflammation, allergic responses, lung cancer proliferation and oral bacterial growth. Cadmium (Cd) is a heavy metal that has been found to cause many toxicities, including liver toxicity. The aim of this study was to evaluate the capacity of 70% ethanol extract of E. umbellata leaves (EUL) to protect human hepatocytes from Cd toxicity. After exposure of HepG2 cells to Cd at 10 𝜇M for 24 h, cell viability, expression levels of apoptosis- and antioxidant-related proteins, reactive oxygen species (ROS) accumulation and Cd uptake were assessed. EUL protected HepG2 cells from Cd-induced apoptosis as determined by MTT assay. A decrease in caspase-3 and p-p53 protein levels was observed in cells pretreated with EUL prior to Cd exposure. Furthermore, the Cd-induced increase in intracellular DCF fluorescence was attenuated by EUL, indicating that the Cd-induced apoptosis preventing effect was associated with the suppression of ROS accumulation. Moreover, EUL's effects on the inhibition of p38, JNK, and AKT phosphorylation also appear to be associated with protection against Cd toxicity. Moreover, EUL upregulated Cd-depressed expression of Nrf2, HO-1, catalase, and MT-1,2 proteins, suggesting that Cd uptake-induced apoptosis in HepG2 cells may be inhibited by EUL's antioxidative potential.

• 한국환경보건학회지
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• 제47권5호
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• pp.446-453
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• 2021

Background: Plastic particles less than 5 mm in diameter (microplastics) are well-known for causing various toxicities such as lung inflammation, oxidative stress, genotoxicity, and reproductive toxicity. As microplastics become smaller, they can move across cell membranes, the placenta, and the blood-brain barrier. Objectives: We evaluated the toxicities of polyethylene microplastics (PE-PMs) in dams and neonates through intragastric intubation of pregnant ICR mice. Methods: Low concentrations (0.01 mg/mouse/day) and high concentrations (0.1 mg/mouse/day) of polyethylene microplastics were administered from the ninth day of pregnancy to postnatal day seven. The control group was administered with distilled water. On the day of sacrifice, the weight of dams and neonates and the organ weight of neonates was measured. Further, acetylcholinesterase levels and glutathione peroxidase levels were evaluated by using a blood sample obtained on the sacrifice day. Results: No significant difference in the number of neonates was found, but the body weight gain of dams was seen to be lower in the low-dose group. On the other hand, we observed a consecutively declining trend in the weight gain and organ weight of neonates among the high-, control, and low-dose groups. Meanwhile, the serum acetylcholinesterase and glutathione peroxidase level were higher in the low-dose group compared to the control group. Further, the dose-dependent accumulation of microplastics in the organs of neonates revealed the transport of plastic particles from dams to their offspring. Conclusions: Although the exact mechanism of toxicity caused by microplastics could not be confirmed, it was validated that exposure to microplastics during pregnancy and lactation causes its migration between generations and accumulation throughout the body. Hence, it is necessary to evaluate the systemic toxicity of microplastics and assessment of co-morbidities such as second-generation toxicity, neurotoxicity, and depression following long-term exposure.

• Tuberculosis and Respiratory Diseases
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• 제41권3호
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• pp.222-230
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• 1994

연구배경 : Paraquat는 광범위 제초제로서 널리 사용하고 있으나, 중독시 치명적인 중독 증상을 일으킨다. 특히 폐에서는 진행성 불가역성 폐섬유종을 일으키는데, 이의 기전으로 산소유리기와 관계가 있으나 아직은 생화학적 기전이 명확하지 않다. paraquat에 의한 산소유리기가 생기면 glutathione의 변화와 G6PDH, SOD, catalase 및 glutathione peroxidase등의 효소 활성의 변화가 생길 것으로 생각되며, 특히 catalase가 많이 관여할 것으로 생각되어진다. 방법 : Catalase 억제제인 aminotriazole을 사용하여 paraquat만 쓰는 것과 paraquat와 aminotriazole을 같이 투여할때 생쥐의 생존율을 알아보고, 실험군을 정상대조군, Group A(aminotriazole투여군), Group B(paraquat 투여군), Group C(paraquat와 amino-triazole 병합투여군) 4군으로 나누어 폐조직에서 glutathione량, G6PDH, SOD, catalase 및 glutathione peroxidase활성도를 측정하여 비교했다. 결과 : Paraquat와 aminotriazole 병합 투여군의 생존율이 paraquat투여군보다 현저히 감소하였고, paraquat 투여로 인하여 폐 glutathione량은 정상대조군에 비해 20%정도 감소 되었으나, aminotriazole의 투여로 인한 폐 glutathione량의 변화는 없었다. Paraquat투여로 폐 SOD, catalase 및 glutathione peroxidase활성이 모두 유의한 감소를 나타냈는데, 특히 catalase가 가장 큰 효소활성 감소를 나타냈으며, paraquat와 aminotriazole병합투여군에서는 catalase와 glutathione peroxidase활성이 paraquat단독투여군에 비하여 유의한 효소활성감소를 나타냈고, SOD는 효소활성의 변화가 감지되지 않았다. 결론 : Paraquat투여시 catalase활성이 유의하게 감소되는 점으로 보아 paraquat독성이 catalase활성과 밀접하게 연관되는 것으로 사료되며, 또한 paraquat의 독성이 aminotriazole의 병합 투여로 더욱 증가되어 나타나는데, 이러한 결과는 aminotriazole투여로 catalase활성의 감소가 크게 나타나나 glutathione량의 변화는 없는 점으로 보아 aminotriazole투여에 의한 paraquat독성의 증가는 총 폐 glutathione량의 변화에 의한 영향보다는 catalase활성감소에 의한 결과로 생각된다. Paraquat와 aminotriazole를 병합 투여하여 catalase활성이 억제되면 증가된 과산화수소로 hydroxyl radicals이 생성되고, 이에 의한 폐 세포손상이 유발되어 나타나는 것으로 사료된다.

• Toxicological Research
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• 제34권4호
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• pp.343-354
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• 2018

Aluminum oxide nanoparticles ($Al_2O_3$ NPs) are among the most widely used nanomaterials; however, relatively little information about their risk identification and assessment is available. In the present study, we aimed to investigate the potential toxicity of $Al_2O_3$ NPs following repeated inhalation exposure in male Sprague-Dawley rats. Rats were exposed to $Al_2O_3$ NPs for 28 days (5 days/week) at doses of 0, 0.2, 1, and $5mg/m^3$ using a nose-only inhalation system. During the experimental period, we evaluated the clinical signs, body weight change, hematological and serum biochemical parameters, necropsy findings, organ weight, and histopathology findings. Additionally, we analyzed the bronchoalveolar lavage fluid (BALF), including differential leukocyte counts, and aluminum contents in the major organs and blood. Aluminum contents were the highest in lung tissues and showed a dose-dependent relationship in the exposure group. Histopathology showed alveolar macrophage accumulation in the lungs of rats in the $5mg/m^3$ group during exposure and recovery. These changes tended to increase at the end of the recovery period. In the BALF analysis, total cell and neutrophil counts and lactate dehydrogenase, tumor necrosis factor-${\alpha}$, and interleukin-6 levels significantly increased in the 1 and $5mg/m^3$ groups during exposure. Under the present experimental conditions, we suggested that the no-observed-adverse-effect level of $Al_2O_3$ NPs in male rats was $1mg/m^3$, and the target organ was the lung.

• 생명과학회지
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• 제13권6호
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• pp.775-781
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• 2003

옻나무(Rhus verniciflua Stokes)로부터 제초제인 paraquat(PQ)의 독성 경감기전을 추구할 목적으로 ethylacetate 분획에서 분리한 fustin 및 sulfuretin을 실험동물에 투여하고서 혈액학적 변화 및 간장 중 활성산소에 미치는 영향 검토한 결과 혈액 생화학적 인자 분석을 종합해 보면 옻나무의 메탄을 엑스(250 mg/kg), 에틸아세테이트 엑스(250 mg/kg), fustin(10 mg/kg) 및 sulfuretin(10 mg/kg)을 2주간 각각 경구투여 하고서 PQ를 투여하므로서 PQ의 독성이 유의성 있게 억제되었다. in vivo에서 옻나무의 분획 및 성분의 투여는 혈액생화학적 검사에서 PQ에 의해 유도된 간독성 지표인 s-GPT, s-GOT치, 신장독성지표인 BUN, creatinine치 및 조직손상의 지표인 ALP, MDA치를 억제하였다 폐조직중의 MDA함량, ALP활성 및 collagen함량도 억제하였다. 이로써 옻나무에는 PQ의 폐독성 및 각 장기의 독성을 효과적으로 경감시켜 줄 수 있는 물질이 함유되어 있는 것으로 사료된다.

• 대한약침학회지
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• 제5권1호
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• pp.27-42
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• 2002

Objective: The purpose of this study was to investigate the acute and subacute toxicity and sarcoma- 180 anti-cancer effects of Herbal acupuncture with Triglii Semen in mice and rats. Method: Balble mice were injected intraperitoneally with Triglii semen Herbal acupuncture for $LD_{50}$ and acute toxicity test. Sprague Dawley rats were injected intraperitoneally with Triglii semen Herbal acupuncture for subacute toxicity test. The Triglii semen Herbal acupuncture was injected on Chung-wan(CV12) of mice with S-180 cancer cell line. Results: 1. In acute toxicity test, the $LD_{50}$ value was $7.49{\times}10^3$ml, 0.30ml/kg.2. The body weights of mice treated with Triglii semen Herbal acupuncture increased during the acute toxicity test. 3. In acute toxicity test of serum biochenrical values of mice, total protein was decreased in treatment groups I, 2 and 3, albunrin was decreased in treatment groups 2 and 3 compared to the control group. GOT was increased in treatment group I and Alk. Phosphatase was increased in treatment groups 1,2 and 3 compared to the normal group(p<0.05). 4.ln subacute toxicity test, severe tissue injury was found in lung and liver. 5. In subacute toxicity test, the body weight was decreased in treatment groups I and 2 compared to the normal group and the weight of liver. lung and kidney were increased in treatment groups 1, 2 and 3 compared to the normal group.(p<0.05) 6. In subacute toxicity test, RBC, HGB and HCT were decreased in treatment groups 1 and 2 compared to the normal group. MCV was increased in treatment group1 compared to the normal group, MCH was increased in treatment groups 1 and 2 compared to the control group in complete blood count test.(p<0.05) 7. In subacute toxicity test, total protein was decreased in treatment groups 1 and 2 compared to the nonnal group, BUN was increased in treatment groups 1 and 2 compared to the nonnal group, creatinine and uric acid were decreased in treatment groups 1 and 2 compared to the normal group, glucose was increased in treatment group 2 compared to the nonnal group, triglycelide was decreased in treatment groups I and 2 compared to the normal group, total cholesterol was increased in treatment groups 1 and 2 compared to the control group. GOT was decreased in treatment group 2 compared to the normal and control group, AIk. Phosphatase was increased in treatment group 1 compared to the normal and control group.(p<0.05) 8. Median survival time was 17days in treatment group 2 for S- 180 cancer cell treated with Triglii semen Herbal acupuncture. 9. Natural killer cell activity was insignificant for S-180 cell treated with Triglii semen Herbal acupuncture.(p<0.05) 10. lnterieukin-2 productivity was decreased for S-180 cell treated with Triglii semen Herbal acupuncture compared to the normal and control group.(p<0.05) Conclusion: According to the results, we can conclude Herbal-acupuncture with Triglii semen caused toxicity, and caused no effects in S-180 cancer cell.

• 한국환경보건학회지
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• 제46권3호
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• pp.312-323
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• 2020

Objective: This study aimed to summarize the physiochemical properties, toxicity, and legal regulation of chloromethylisothiazolinone (CMIT) and/or methylisothiazolinone (MIT), review the health effects caused by exposure to CMIT/MIT, and evaluate the individual association of lung injury with the use of humidifier disinfectants (HD) containing a mixture of CMIT and MIT. Method: A literature review was conducted by searching keywords such as CMIT, MIT, health effect, dermatitis, asthma, and lung injury, either singly or combined. Results: Both CMIT and/or MIT were found to be associated with the development of several types of adverse health effects. In particular, respiratory diseases including asthma, nasal symptoms, cough, and rhinitis were caused by the use of products including CMIT or/and MIT. The mixture of CMIT/MIT has been banned in cosmetics. As of the end of 2017, nine patients who were confirmed to have HD associated lung injury (HDLI) were found to have used only an HD brand containing CMIT and MIT. Their responses regarding the name of the HD used could be trustworthy based on the short duration of HD use (less than six months) before the onset of HDLI and frequent use of HD per day. Conclusion: According to the toxicity and HDLI cases, the use of HD containing CMIT and /or MIT can cause fatal lung injury. Further study with manufacturers' assistance is necessary in order to obtain more clear evidence on the causal relationship since HDLI cases are being reported continuously.

• 한국환경보건학회지
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• 제38권2호
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• pp.166-174
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• 2012

Introduction: After 17 years since the first production of humidifier disinfectants in Korea, Korea Centers for Disease Control and Prevention (KCDC) announced that the odds ratio of lung injury related with humidifier disinfectant usage was 47.3 (95% confidence interval 6.0-369.7) according to a case-control study with 18 adult cases, including 8 pregnant women at a university hospital in Seoul. Results: From September 2011 to April 2012, one-hundred and seventy four victim cases have been reported to an environmental non-governmental group (NGO). We summarized timetable of humidifier disinfectants accidents, analyzed health outcomes (death, lung or lung and heart transplantation, pulmonary disease) of reported victims, and classified some information for humidifier disinfectants with health outcomes, and government action for this accident. Among the victims, number of death cases are 52 (30.0%), including 26 babies less than 3 years old. Sixty-nine victims come from twenty-seven family with 2 to 4 members per family. About twenty types of humidifier disinfectant products and about 600,000 product items a year have been sold. Fifty-two death cases used 7 different types of disinfectant products, including imported goods and some private brands of well-known supermarkets. KCDC confirmed inhalation toxicity of 6 products through an animal experimental test, and based on this observation recalled disinfectants containing PHMG (polyhexamethylene guanidine) and PGH (Oligo(2-(2-ethoxy)ethoxyethyl guanidinium chloride). Discussions: The use of these biocides involved highly fatal consequences among biologically vulnerable victims, such as pregnant women, several family member victims after semi-acute exposure. This is the first biocide disaster in Korea with non-specific targets, and unknown scale of victims, warranting concerns on use of biocides in the living environment. Conclusions: Special administrative agency for chemical safety and compensation act for environmental health victims are needed to prevent similar problems.

• Asian Pacific Journal of Cancer Prevention
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• 제13권9호
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• pp.4703-4706
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• 2012

Objective: To compare efficacy and safety profile of vinorelbine, ifosfamide and cisplatin (NIP) with etoposide and cisplatin (EP) in the treatment of advanced combined small cell lung cancer (c-SCLC). Methods: From January 2006 to December 2010, 176 patients with advanced c-SCLC were enrolled. The primary endpoint was overall survival (OS) and the secondary endpoints were progression free survival (PFS), response rate (RR) and toxicity. Results: Overall RR was 30.0% in the NIP and 38.5% in the EP group; there was no significant difference (P=0.236). The PFS in the EP group was little longer than that of NIP group, with 6.5 months for EP and 6.0 months for NIP group, but the difference was statistically non-significant (P=0.163). The median OS and one year survival rates were 10.4 months and 36.3% for NIP group, and 10.8 months and 49.0% for EP respectively, EP showing a survival benefit, although this was not statistically significant. Both groups well tolerated the adverse effects. The incidence of grade I-II leucopenia and alopecia in the NIP group was significantly higher than that of EP group (32.5% vs. 10.4% (P<0.001, 35.0% vs. 12.5%, P<0.001). Conclusion: the ORR, PFS and OS in NIP were slightly inferior to traditional regimen EP. The toxicity of NIP can be considered tolerable. The usage of three drugs combination in the treatment of mixed SCLC remains uncertain. Nevertheless, the results need to be further confirmed by large, prospective clinical trials.