Joint toxic action of binary metal mixtures of copper, manganese and nickel to Paronychiurus kimi (Collembola)

Son, J.,Lee, Y.s.,Kim, Y.,Shin, K.i.,Hyun, S.,Cho, K. Academic Press 2016 Ecotoxicology and environmental safety Vol.132 No.-

<P>The joint toxic effects of binary metal mixtures of copper (Cu), manganese (Mn) and nickel (Ni) on reproduction of Paronhchiurus kimi (Lee) was evaluated using a toxic unit (TU) approach by judging additivity across a range of effect levels (10-90%). For all metal mixtures, the joint toxic effects of metal mixtures on reproduction of P. kimi decreased in a TU-dependent manner. The joint toxic effects of metal mixtures also changed from less than additive to more than additive at an effect level lower than or equal to 50%, while a more than additive toxic effects were apparent at higher effect levels. These results indicate that the joint toxicity of metal mixtures is substantially different from that of individual metals based on additivity. Moreover, the close relationship of toxicity to effect level suggests that it is necessary to encompass a whole range of effect levels rather than a specific effect level when judging mixture toxicity. In conclusion, the less than additive toxicity at low effect levels suggests that the additivity assumption is sufficiently conservative to warrant predicting joint toxicity of metal mixtures, which may give an additional margin of safety when setting soil quality standards for ecological risk assessment (C) 2016 Published by Elsevier Inc.</P>

The Antioxidative Effect of Eclipta prostrata L. Extract on Cultured NIH3T3 Fibroblasts Injured by Manganese-Induced Cytotoxicity

Sang-Hee Lee,In-Ju Jung,Hyesook Jang 대한의생명과학회 2018 Biomedical Science Letters Vol.24 No.4

Manganese (Mn) is used as main materials in various chemical processes of industry, but it suggested that Mn brings about its toxicant by fume or dust through respiratory system and skin barrier. Mn toxicant induces the loss of mental health and life quality by cerebrovascular and skin diseases. Nevertheless, it lefts much unknown on the mechanism and the effectively therapeutic methods about Mn toxicant. Therefore, this study was evaluated the cytotoxicity induced by manganese dioxide (MnO₂) in cultured NIH3T3 fibroblasts, and also, the correlation between MnO₂-induced cytotoxicity and oxidative stress was examined. While, the effect of Eclipta prostrata L. (EP) extract belong to Compositae was assessed against MnO₂-induced cytotoxicity in the view of antioxidative effect for searching the natural resources mitigating or preventing the MnO₂-induced cytotoxicity. In this study, MnO₂-induced cytotoxicity was revealed as mid-toxic by Borenfreud and Puerner`s toxic criteria, and catalase (CAT), an antioxidant prevented MnO₂-induced cytotoxicity by the remarkable increase of cell viability in these cultures. While, in the protective effect of EP extract on MnO₂-induced cytotoxicity, EP extract effectively prevented the cytotoxicity induced by MnO₂ via antioxidative effects such as xanthine oxidase (XO) inhibitory ability and DPPH-radical scavenging ability. From the above results, EP extract showed the effective prevention against MnO₂-induced cytotoxicity correlated with oxidative stress by antioxidative effects. Conclusively, this study may be useful to research or development the alternatively therapeutic agent from natural resources like EP extract for the treatment of diseases resulted in oxidative stress.

Testicular Cytotoxicity of Anticancer Chemotherapeutic Drugs and Protective Effect by a Gonadotropin-Releasing Hormone Analgue in

Park, Yong Hyun,Kim, Sae Woong CATHOLIC MEDICAL CENTER 1988 Bulletin of the Clinical Research Institute Vol.16/17 No.1

Many studies of testicular toxicity by several anticancer chemotherapeutic drugs and protective effect of testicular toxicity by a gonadotropin-releasing hormone analogue have been performed in mice but protective effect of testicular toxicity by a gonadotropin-releasing hormone analogue is still controversial. In this study mature male (Charles River Japan Inc.) mice,8-12 weeks of age, weghing 20-25g were used to evaluate not only testicular toxicity by adriamycin, thio-TEPA, cis-platinum, vinblastine, mitomycin C, methotrexate and bleomycin but also protective effect of testicular toxicity by a gonadotropin-releasing hormone analogue in adriamycin and thio-TEPA. Each drug was administered with LD50 1/10 and LD50 1/2 dose as singly intraperitoneal injection. Pretreatment and continued administration of gonadotropin-releasing hormone analogue was done in adriamycin and thio-TEPA administered with LD50 dose. On the 50th day after administration of anticancer chemotherapeutic drugs, all surviving mice were killed and necropsied. Testicular toxicity by several anticancer chemotherapeutic drugs and protective effect of testicular toxicity by a gonadotropin-releasing hormone analogue were evaluated by testicular weight, Repopulation Index and histology. The results were as follows: 1. All group administered with LD50 1/10 dose showed statistical decrease in testicular weight compared to control group. Repopulation Index was decreased statistically in the group of adriamycin and thio-TEPA compared to control group. 2. All groups administered with LD50 1/2 dose showed statistal decrease in testicular weight compared to control group. Repopulation Index was decreased statistically in the groups of adriamycin and thio-TEPA compared to control group. Testicular weight and Repopulation Index were decreased in the groups with LD50 1/2 dose more than the other ones with LD50 1/10 dose. 3. All groups administered with LD50 1/10 dose showed a decrease in the number and thickness of semineferous tubules and an increase in the number of empty tubules. The pathologic finding of testis were increased in the groups with LD50 1/2 dose more than the other ones with LD50 1/10 dose. The number of empty tubules was significantly increased in the groups of adriamycin and thio-TEPA compared to control group. 4. In adriamycin and thio-TEPA administered with LD50 dose, testicular weight and Repopulation Index were increased statistically in the groups tented with gonadotropin-releasing hormone analogue compared to non-treated groups. 5. In adriamycin and thio-TEPA administered with LD50 dose, the histologic improvement of spermatogenesis was present in the groups treated with gonadotropin-releasing hormone analogue compared to non-treated groups. In conclusion, adriamycin and thio-TEPA induced serious toxic effect in the testicular stem cell of mouse and the treatment of gonadotropinreleasing hormone analogue produced striking protection for adriamycin and thio-TEPA induced testicular toxicity.

발광박테리아 Vibrio fischeri를 이용한 과불화합물과 중금속의 복합독성평가

이우미(Woo Mi Lee),김지성(Ji Sung Kim),김일호(Il Ho Kim),김석구(Seog Ku Kim),윤영한(Young Han Yoon) 大韓環境工學會 2014 대한환경공학회지 Vol.36 No.2

본 연구에서는 과불화합물(PFOA, PFOS)과 수계에 보편적으로 존재하는 중금속(Cu, Zn, Cr, Cd, Pb, Hg)의 복합독성을Vibrio fischeri를 이용하여 평가하였다. PFOA와 PFOS의 경우, 30 min-EC50값이 각각 134.21 (119.54-150.68)와 235.97 (180.96-307.70) mg/L로 PFOS 보다는 PFOA의 독성이 높은 것으로 나타났다. 한편 중금속류의 독성은 Hg2+의 독성이 가장 높았으며, 이어서 Pb2+, Cr6+, Cu2+, Zn2+, Cd2+ 순으로 높은 독성민감도를 나타냈다. 과불화합물류와 중 금속류의 복합독성의 경우, PFOA와 PFOS 모두 Cr6+과 공존할 시 상승효과가 나타났으며, PFOA + Zn2+, PFOS + Zn2, PFOA + Cd2+, PFOS + Cd2+의 조합은 상가효과를 나타냈다. 이외의 복합물질은 모두 길항작용을 하는 것으로 확인되었다. 본 연구에서는 과불화합물인 PFOA, PFOS와중금속 복합물질들의 조합에 따른 상호작용이 상이함을 확인하였고 이 결과로부터 과불화합물과 중금속 공존할 때 수환경에 야기할 수 있는 잠재적 위해성을 예측할 수 있다. The object of this study was to evaluate the combined toxic interactions of the perfluorooctanoic acid (PFOA) or per-fluorooctane sulfonate (PFOS) with six heavy metals (Cu, Zn, Cr, Cd, Hg, and Pb). The individual and combined toxic effects wereassessed using the Vibrio fischeri assay. In case of the individual toxicity, PFOA was higher toxic than PFOS and toxicity of PFOA and PFOS were lower than heavy metal. In the toxicity of heavy metals, the Hg2+ was found to be most toxic followed byPb2+, Cr6+, Cu2+, Zn2+, and Cd2+. The combined toxicity of PFOA or PFOS with Cr6+ were synergistic effect because the EC50mixvalues were less than 1 TU. PFOA + Zn2+, PFOS + Zn2+, PFOA + Cd2+ and PFOS + Cd2+ produced addictive effect. Except in these case, all of binary mixtures show antagonistic effect. This study proved potential risk of coexistent with perfluorinated compounds and heavy metals in water environment.

산양산삼 추출액의 항암효과 및 Doxorubicin에 의한 고환독성 방어효과

민병일,김호현,서일복,권기록,Min, Byung-Il,Kim, Ho-Hyun,Seo, Il-Bok,Kwon, Ki-Rok 대한약침학회 2007 Journal of pharmacopuncture Vol.10 No.1

Objectives : This research was executed to verify antitumor effect and protective effect on doxorubicin(Doxo)-induced toxicity of Cultivated Wild Ginseng(CWG) and synergic effect of CWG with Doxo in B16/F10 melanomas-bearing C57BL/6 mice. Methods : To evaluate protective effect on doxorubicin(Doxo)-induced toxicity and enhancing effect on the antitumor activity of Doxo, CWG water extract(0.5 ml) was intraperitoneally injected for 10 days, in combination with intraperitoneal injection of Doxo(4 mg/kg) on days 12, 16, 19, to mice subcutaneously inoculated with $2{\times}10^6/ml$ B16/F10 melanoma cells. In order to investigate antitumor effect of CWG, CWG water extract(0.5 ml) was intraperitoneally injected for 10 days to mice subcutaneously inoculated with $2{\times}10^6/ml$ B16/F10 melanoma cells. Results : The body weights of melanoma-bearing mice increased following B16/F10 cells inoculation. In contrast, such an increase in body weights was significantly attenuated by Doxo administration. Whereas CWG inhibits the decrease in body weights induced by Doxo. The tumor volume and tumor weights of melanomas-bearing mice dramatically increased following B16/F10 cells inoculation, In contrast, such an increase in tumor volume and tumor weights were significantly attenuated by Doxo or CWG administration. But the synergic effect of CWG with Doxo was not observed. The reduction of cellularity of seminiferous epithelia, level of spermatogonium and spermatid induced by Doxo was recovered by CWG administration. BrdU labeling index of spermatogonium was remarkably decreased in Doxo group but was no change in CWG group. Whereas the incidence and intensity of BrdU labelled spermatocytes and spermatids were increased by CWG administration than those of Doxo group. Conclusions : The obtained results suggest that CWG have antitumor effect and protective effect on doxo-induced testicular toxicity. This effect might be mediated through the supplementation of vital energy.

산소중독에 대한 MALTOL의 보호효과에 관한 실험적 연구

황성주,조수헌,윤덕로,Hwang, Sung-Joo,Cho, Soo-Hon,Yon, Dork-Ro 대한예방의학회 1993 Journal of Preventive Medicine and Public Health Vol.26 No.4

Since the widespread application of hyperbaric oxygenation in clinical medicine, the problems of oxygen toxicity have been attracting a deep interest from the researchers on hyperbaric medicine as a practical issue. Among extensive research trials, the study on the protective agents oxygen toxicity occupied one of the most challenging field. As the mechanisms of oxygen toxicity, the role of the oxygen free radicals produced by peroxidation process are strongly accepted by the leading researchers on oxygen toxicity, the probable protective effects of antioxidant against oxygen toxicity are sustaining a sufficient rational. Maltol ($2-methyl-3-hydroxy-{\gamma}-pyrone$) which is known to be a component of Korean red ginseng has been reporting to have an antioxidant action. But, further study is needed to provide definite evidence for this compound to be an antioxidant, since the action was based on the results which were obtained under in vitro experiment. In this study, the author attempted to evaluate the effect of maltol as protective agent against oxygen toxicity through the observation of death rate, convulsion rate, time to convulsion and microscopic pathological changes in some organs of experimental rats exposed to various conditions. The findings observed are as follows : 1) The death rate, convulsion rate, time to convulsion, lung/weight ratio and microscopic pathological finding of lung were identified as reliable objective and quantitative indices for oxygen toxicity. 2) Maltol showed excellent protective effect against pulmonary oxygen toxicity as an antioxidant.

Cost-effectiveness of Non-steroidal Anti-inflammatory Drugs Adjusting for Upper and Lower Gastrointestinal Toxicities in Rheumatoid Arthritis Patients

( Soo-jin Chung ),( Hye-jin Park ),( Min-chan Park ) 대한류마티스학회 2017 대한류마티스학회지 Vol.24 No.1

Objective. This study was performed to assess the cost-effectiveness of cyclooxygenase-2 (COX2)-selective inhibitor, non-selective non-steroidal anti-inflammatory drugs (NSAIDs), and non-selective NSAID with proton pump inhibitors (PPIs) while considering upper and lower gastrointestinal (GI) safety in patients with rheumatoid arthritis (RA). Methods. A Markov model was used to estimate the costs and effectiveness. Estimates of therapeutic efficacy and upper/lower GI safety were based on results from large randomized controlled trials. The main outcome measure was cost effectiveness, based on the quality-adjusted life years (QALYs) gained. Safety parameters included clinical upper GI symptoms, uncomplicated ulcer, upper GI bleeding, upper GI perforation, clinical lower GI symptoms, lower GI bleeding, and lower GI perforation. Cost data were obtained from patients treated in a tertiary referral center in Korea. Results. The expected three year cost was 3,052,800 Korean won (KRW) for COX2-selective inhibitor, 3,170,800 KRW for nonselective NSAID, and 3,325,900 KRW for non-selective NSAID with PPI. QALYs were 2.87446, 2.85320, and 2.85815, respectively. The total cost for COX2-selective inhibitor use was lower than non-selective NSAID, but QALY was higher, indicating that the incremental cost effectiveness ratio of COX2-selective inhibitor is superior. Conclusion. COX2-selective inhibitor has reasonable cost-effectiveness adjusted for upper and lower GI toxicity for patients with RA in Korea. (J Rheum Dis 2017;24:27-34)

B103 세포에서 베타아밀로이드(25-35) 독성에 대한 Ginsenoside Rb_l과 Rg_l의 보호효과

이은아,주인수,허균,묵인희 대한신경과학회 1999 대한신경과학회지 Vol.17 No.5

Protective effect of Jageum-Jung on chlorpyrifos-induced acute toxicity in ICR mice

( Nam-hui Yim ),( Jin Yeul Ma ) 한국응용생명화학회(구 한국농화학회) 2018 Journal of Applied Biological Chemistry (J. Appl. Vol.61 No.4

Chlorpyrifos (CPF) is one of the most heavily used organophosphate pesticides and is useful as an insecticide drug. However, CPF also causes toxic effects in nontarget organisms, including humans and animals. Jageum-Jung (JGJ) is a traditional oriental medicine, composed of five specific herbs with antioxidant and hepatoprotective properties, used for detoxification. In the present study, highly concentrated CPF was orally administrated to male Institute of Cancer Research mice to produce acute toxicity, and the protective effects of JGJ administration were investigated through statistical analysis of changes in body and organ weights and serum biochemical parameters. JGJ caused body and organ weights to recover and reduced the levels of serum biochemical parameters indicative of liver damage, such as glutamic oxalate transaminase, glutamic pyruvate transaminase, alkaline phosphatase, lactic dehydrogenase, urea, glucose, total cholesterol, and triglyceride, that had been increased by CPF treatment. Our results demonstrated that JGJ ameliorates the effects of acute chlorpyrifos-induced toxicity. Therefore, JGJ has the potential to be used as a traditional medicine to alleviate insecticide toxicity.

총설 : 파라벤류의 독성과 내분비계장애 효과

안혜선 ( Hae Sun Ahn ),나원흠 ( Won Heum Nah ),이재은 ( Jae Eun Lee ),오영석 ( Yeong Seok Oh ),계명찬 ( Myung Chan Gye ) 한국환경생물학회 2009 환경생물 : 환경생물학회지 Vol.27 No.4

파라벤은 p-하이드록시 벤조산(p-hydroxybenzoic acid)의 알킬에스테르로, 비교적 빠르게 흡수, 대사 및 배설되는 살균성 보존제로 식품, 화장품, 약품 등에 널리 사용되고 있다. 실제 인체는 파라벤 복합물에 노출된다. 파라벤의 안전성에 관한 연구결과들에 대한 고찰 결과 파라벤 종류에 따라 다양한 독성종말점을 대상으로 파라벤의 급성, 아급성 및 만성독성 영향은 비교적 적은 것으로 나타났다. 파라벤은 에스트로젠 유사활성을 가지며 화장품을 통한 경피흡수를 통해 유방암과의 상관성이 보고되었으나, 이와 상반된 견해도 있다. 파라벤의 항안드로젠성은 남성생식기계의 장애를 유발할 수 있으나 이와 상반된 견해도 있다. 파라벤은 정자의 미토콘드리아 기능 및 남성호르몬 생성을 저해할 수 있으나 이와 상반된 견해도 있다. 배아발달에는 독성이 없는 것으로 나타났다. 세포독성으로는 세포용혈, 미토콘드리아 막투과성변화, 세포사멸 등을 유발할 수 있다. 수환경에서 파라벤은 환경에스트로젠으로 작동하여 어류에서 내분비장애 효과를 발휘한다. 결론적으로 파라벤은 저독성물질로 분류할 수 있으나, 인체 및 수생동물들에서 파라벤의 노출경로 및 농도, 사용기간 등에 따른 독성과 내분비계장애 효과에 대하여는 다양한 종말점을 대상으로 좀 더 구체적인 독성자료들이 요구된다. Parabens are alkyl esters of p-hydroxybenzoic acid, which are widely used in foods, cosmetics, and pharmaceutic products as preservatives. Absorbed parabens are metabolized fastly and excreted. Actually human body is exposed to complex mixture of parabens. Safety assessment at various toxicological end points revealed parabens have a little acute, subacute and chronic toxicities. Some reports have argued that as parabens have estrogenic activity, they are associated with the incidence of breast cancer through dermal absorption by cosmetics. There is an inference that antiandrogenic activity of parabens may give rise to a lesion of male reproductive system, but also there is an contrary. At cellular level, parabens may inhibit mitochondrial function of sperms and androgen production in testis, but also there is an contrary. Parabens seem to have little or no toxicity in embryonic development. Parabens can cause hemolysis, membrane permeability change in mitochondria and apoptosis, suggesting cellular toxicity of parabens. Parabens evoked endocrine disruption in several fish species and have toxic effect on small invertebrates and microbes. Therefore, the toxicity of parabens should be considered as a potentially toxic chemical in the freshwater environment. In conclusion, though parabens may be considered as a low toxic chemical, more definite data are required concerning the endocrine disrupting effect of parabens on human body and aquatic animals according to route and term of exposure as well as the residual concentration of parabens.