• Development and Reproduction
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• v.19 no.4
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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.

• Food Science and Preservation
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• v.30 no.5
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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.

• Journal of Environmental Health Sciences
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• v.47 no.5
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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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• v.41 no.3
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• pp.222-230
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• 1994

Background: Paraquat, a widely used herbicide, is extremely toxic, causing multiple organ failure in humans. Paraquat especially leads to irreversible progressive pulmonary fibrosis, which is related to oxygen free radicals. However, its biochemical mechanism is not clear. Natural mechanisms that prevent damage from oxygen free radicals include changes in glutathione level, G6PDH, superoxide dismutase(SOD), catalase, and glutathione peroxidase. The authors think catalase is closely related to paraquat toxicity in the lungs Method: The effects of 3-amino-1,2,4-triazole(aminotriazole), a catalase inhibitor, on mice administered with paraquat were investigated. We studied the effects of aminotriazole on the survival of mice administered with paraquat, by comparing life spans between the group to which paraquat had been administered and the group to which a combination of paraquat and aminotriazole had been administered. We measured glutathion level, glucose 6-phosphate dehydrogenase(G6PDH), superoxide dismutase(SOD), catalase, and glutathione peroxidase(GPx) in the lung tissue of 4 groups of mice: the control group, group A(aminotriazole injected), group B(paraquat administered), group C(paraquat and aminotriazole administered). Results: The mortality of mice administered with paraquat which were treated with aminotriazole was significantly increased compared with those of mice not treated with aminotriazole. Glutathione level in group B was decreased by 20%, a significant decrease compared with the control group. However, this level was not changed by the administration of aminotriazole(group C). The activity of G6PDH in all groups was not significantly changed compared with the control group. The activities of SOD, catalase, and glutathione peroxidase(GPx) in the lung tissue were significantly decreased by paraquat administration(group B); catalase showed the largest decrease. Catalase and GPX were significantly decreased by aminotriazole treatment in mice administered with paraquat but change in SOD activity was not significant(group C). Conclusion: Decrease in catalase activity by paraquat suggests that paraquat toxicity in the lungs is closely related to catalase activity. Paraquat toxicity in mice is enhanced by aminotriazole administration, and its result is related to the decrease of catalase activity rather than glutathione level in the lungs. Production of hydroxyl radicals, the most reactive oxygen metabolite, is accelerated due to increased hydrogen peroxide by catalase inhibition and the lung damage probably results from nonspecific tissue injury of hydroxyl radicals.

• Toxicological Research
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• v.34 no.4
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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.

• Journal of Life Science
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• v.13 no.6
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• pp.775-781
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• 2003

In this study, we investigated to elevate the modulatory effect of flavonoid(fustin, sulfuretin, 10 mg/kg) which was isolated from Rhus verniciflua Stokes(RVS) in male Sprague-Dawley rats for 2 weeks on the toxicity of paraquat. In the flavonoids pretreated groups, glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, blood urea nitrogen, creatinine, malondialdehyde and alkaline phosphatase activity in serum and malondialdehyde, alkaline phosphatase activity and collagen in lung tissue which was induced paraquat toxicity were slightly decrease compared to the normal group. In the lung tissue of flavonoids pretreated groups, malodialdehyde value, G-6-phosphatase activity and collagen synthesis were recovered to tile normal values and alkaline phosphatase activity was increased. From these results, we concluded that flavonoids which were isolated from RVS is an effective agent to inhibit the pulmonary and internal toxicities and hence we concluded that acitive components of fustin and sulfuretin which were isolated from RVS might be removed free radicals induced by paraquat.

• Journal of Pharmacopuncture
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• v.5 no.1 s.8
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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.

• Journal of Environmental Health Sciences
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• v.46 no.3
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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.

• Journal of Environmental Health Sciences
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• v.38 no.2
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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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• v.13 no.9
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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.